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·Treatment of
BREAST TUMORS
Robert S Pollack, MD, FACS
Clinical Instructor in Surgery Stanford Unlocrsity School of
Medicine Clinical Instructor in Surgery (Oncology) Unicer
dty of California School of Vedicine Apletant Chict of
Surgery Slount Zton Hopital San Francisco, Callfornia
Consulting Surgeon Oakland Veterans Administration
Hospital Consulting Surgeon, Oakland local Hospital
Oalland Callfornia
47 Plates and 16 Text Figures
Lea & Febiger
Phuadelphia
1038

·Library of Congress Card Catalog Number
58-13031
Printed in The United States of America

·CONTRIBUTORS Adrenalectomy Donald E. Bernstoin, M.D Arddant Clinical Profesor of Vedicine Stanford Unloersity School of Medicine Gerson R. Biskund, MD Ausletant Clinical Profesor of Pathology Untoernity of California School of Medicine Pathologic Classification of Breast Tumors Medical Treatment of Chronic Cystic Mastitas Hypophysectomy Francis S Greenspan, MD Autoclato Clinical Profesor of Medicine Stanford Untcerotty School of Bledicine Trans sphenoidal Hypophygectomy Walter E. Heck, V.D Associate Professor of Otorhinolaryngology Stenford University School of diedidno Oral and Parenteral Honnones Nicholas L. Petrakıs, M.D Assistant Professor of Vedicino Unloorsity of California School of Bediano Radiotherapy of Breast Cancer Gcorgo W Reimer, MD Indructor in Rodiology, Stonford Unlocritty School of Medictho Robert ) Schweitzer MD Attonding Surgron Veterans Adminletra tlon Hospital Oshland California, and Staff Surgeon, Oakland, California Hospitals Results of Surgery And Effect of Special Factors on Results Extended Radical Minstectomy (6)

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·PREFACE It is hoped that this book will bring together many loose ends regarding the diagnosis and treatment of breast cancer For such a large topic brevity and conciseness which have been major aims, were hard to maintain, yet have been accomplished The practicing physician today is faced with a plethom of infor mation regarding breast cancer He may even fcel that despite his most conscien tious efforts his progrm of thempy lacks something, is old fashioned or unnecessary The general paturo of breast cancer itself tends to enhance this feeling Certainly it is a disease whuch occupies a Leystone position in the hormone dependent group of cancers It also is responsive to Irradiation therapy Its method of operative treatment represents a major tenet of cancer surgery In addition to all this noter concepts of hormone physiology radiation therapy And surgical techniques have added to the complexity of trentment It is the purpose of this book to broaden our knowledge of breast cancer first by presenting a brief classification of breast tumors, and then discussing the diagnosis treatment and complications of both benign and malignant breast tumors in the light of histology and never concepts of therapy Special sections on radiotherapy results of treatment, the extended radical mastectomy and treatment by hormone alteration follow to complete the picture without omission of the main theme to renew yet reaflirm the practicing physicians basic knowl edgo and methods. To my close friends and colleagues, who have added so much to this book by their collaboration, I offer my thanks I wish also to express my gratitude to the members of the Tumor Boards of the Stanford Unhersity Hospital, San Francisco Califomla and of the Veterans Administration Hospital and the US Naval Hospital, Oakland, California whose constant presentation of cases and discus Chile G1 Cancer of the Breast Tho Surgeons Dienne, Cleveland Clinic Quarterly 23 179 1058

·8
Preface
sions added so much to my own knowledge and experience, and to Grant
Levin, MD, neurosurgeon, for his suggestions regarding the chapter on
hypophysectomy
Indeed, I would be greatly remiss if I were not to thank Miss Kay Hyde whose
painstaking drawings have added inestimable value and interest to this book,
my secretary, Mrs Ernestine Stotler, for her cheerful labors in expertly typing
and ietyping the manuscript, and finally, the publishers, Lea & Febiger, for their
help and cooperation
ROBERT S POLLACK, MD
SAN FRANCISCO, CALIFORNIA

·CONTENTS CHAPTER PACE 1 Introduction 11 2. Pathologic Classification of Breast Tumors 12 18 19 21 27 30 33 3 Benign Tumors of the Breast Chronic Cystic Alastitis Surgical Technique of Excisional Blopay Medical Treatment of Chronic Cystic Vlastitis Chronic Cystic Viestitis and Cancer Papillomas of the Duct Surgical Techniquo of Resection of Papillomas of the Duct Fibroadenomas Cystosarcoma Phyllodes Allscellaneous Tumors Liporas Fat Necrosis Accessory drammary Tissue 35 41 49 46 46 46 46 47 48 4 Gynecomastia Surgical Technique of Treating Gynecomastia 5 Spontaneous Abscesses and Draining Sinuses Surgical Technique of Treatlog Draming Sinuses 53 53 6 Breast Cancer Diagnosis Operability Lymphatic Drainage of the Breast Choice of Operation Surgical Techniques of Stople Alodified, and Radical Vlastectomy Postoperative Care and Complications 58 59 59 61 62 65 78 (9) ·10 Contents CHAPTER PAGE Postoperative X-ray Therapy Adjunctive Procedures Arm Lymphedema Postoperative Pregnancy The Opposite Bieast Tieatment of Recuiiences Cancer of the Male Breast 79 80 81 82 83 84 85 7. Results of Surgery and Effect of Special Factors on Results 88 8 Extended Radical Mastectomy Surgical Technique 94 96 102 102 9 Radiotherapy of Breast Cancer Physical Considerations of Radiation Relevant to Breast Cancer Biological Considerations of Irradiation of Breast Cancei The Regional Spread of Bieast Cancei Treatment of Breast Cancer with Iuadiation Palliation of Breast Cancer by Iriadiation 103 106 108 116 10. Treatment of Metastatic Breast Cancer by Oophorectomy, Hormones and Chemotherapy 122 129 131 132 11 Adrenalectomy and Metastatic Breast Cancer Pre- and Postoperative Management Surgical Technique of Adrenalectomy 12 Hypophysectomy and Metastatic Breast Cancer Hormonal Management of the Patient Undergoing Surgical Hypophysectomy 139 140 ·Chapter 1 INTRODUCTION WITHOUT resorting to published statistics It is apparent that tumors of the breast occur frequently enough to occupy a significant place in the practicing physician s daily work be he mternist surgeon or general practitioner Adding to deep psychological fears any breast lump will cause m the mind of the Average woman, current lay educational trends create concern and anxiety Because of this the patient rushes to her doctor expecting not only reassurance but also action on the part of her physician which will restore her to health Unfortunately the perplexities of breast tumors, and especially cancer often preclude a wholly confident approach on the part of the physician. Yet there are procedures and methods which through years of experience have proved generally to be reliable and are recommended as the measures to take No treatment can begin without a specific diagnosis and since a lump in the breast may be one of many types the primary step is biopsy Although statisti cally the chances of such a lump n the average middle aged woman, being malignant are less than fts being benign, histologic verification must be obtainod On the other hand, indiscriminato biopsy of every lump should be avoided. The Art and science of physical diagnosis is still to be pursued. Once diagnosts is established methodology becomes all important as a success ful outcome may very well depend on the techniques applied. Following the initial definitive Surgery there will be other considerations such as I may therapy oophorectomny pregnancy and management of the opposite breast, all of which must thon bo weighed in the light of the circumstances and conditions at hand. In breast cancer there are many factors which influence the ultimate result. One, therefore considers the patient as a whole in addition to the specific organ involved. Durtng the life cycle or natural history of a patient with breast cancer at may bocome apparent that despite loitral therapy the patient is doomed and the result, from the standpoint of cure a failure Even then there are steps to take which will increase longevity in comfort and reduce pain and morbidity This later stage of breast cancer may be called the "physiologically therapeutic," in contradistinction to the initial or early stage which is called the "anatomically therapeutic. Since the overall purpose of the practicing physician is to cure and alleviate, each of these stages is considered of equal importance. (11) ·Chapter 2 PATHOLOGIC CLASSIFICATION OF BREAST TUMORS THE following classification of tumors of the breast includes the great majority encountered in daily practice I. Breast Tumors A Benign 1 Encapsulated a) Solid 1) Fibroadenoma 2) Periductal fibroma b) Cystic (pseudo-encapsulated) 1) Simple cyst-single or multiple 2) Benign papillomatous cyst 2 Non-encapsulated a) Intraductal papilloma b) Cystadenoma c) Granular cell myoblastoma B Malignant 1 Ductal origin a) Malignant intraductal papillary carcinoma b) Malignant intracystic papillary carcinoma c) Carcinoma-ductal type including comedocarcinoma 1) Malignant extension to nipple-Paget's disease 2 Glandular origin a) Lobular carcinoma in situ b) Carcinoma-scirrhous, papillary, medullary, colloid or mucoid 3 Mesenchymal tumois a) Lobular carcinoma in situ 1) Benign form 2) Malignant form-sarcoma or carcinoma b) Lymphosarcoma c) Sarcoma II Hypertiophies and related conditions A Focal interstitial fibrosis 1 With glandular hyperplasia 2 With ductal ectasia (comedo-mastitis) B Focal glandular hyperplasia C Gynecomastia III Inflammations A Acute 1 Diffuse 2 Focal B Chronic C Fat necrosis IV Anomalies ·Pathologic Clasification of Breast Tumor 13 Fic 1 --Sclerosing adenomatosis, florid type Distortion of a hyperplastic lobule by denso scar tisic Approx/mately 175 x The gross appearance of the average carcinoma is distinctive and rarely con fused with the focal hypertrophies however it is closely simulated by sclerosing adenomatosis granular cell myoblastoma and chronic fat necrosis Carcinoma has a central grayish white zone of almost cartilaginous hardness when pressed with the top of a dissectiog needle the entire mass is depressed. There are minute grayish white plugs in the mass The edges are poorly defined as a result of the extension of the neoplasm foto adjacent breast parenchyma and fat The ductal carcinomas are limited to ducts which grossly appear ectatic and have minimally thickened walls without gross infiltration of surrounding paren chyma Gross papillary projections and papillomata may be noted in some instances of comcdo-mastitis as well as in ductal carcinoma. Focal interstitial Abrosis with and without glandular hypertrophy and hyper plasia offers the greatest difficulty in the gross differential diagnosis a form of active glandular proliferation combined with Abrosis, commonly called sclerosing adenosis or adenomatosis closely resembles carcinoma in gross appearance (Fig 1) Even after detailed histologic examination it is often difficult to be certain that tho lesion is not a carcinoma ·14 Pathologic Classification of Breast Tumors lo Lir FIG 2-Benign intraductal papillomatosis spreading throughout a group of ducts in a lobule The epithelial cells are small and regular Approximately 175 X A variety of lesions are grouped in the hypertrophies The most common of these are so-called blue dome cysts frequently associated with an increase in the amount of fibrous tissue in the adjacent parenchyma Usually, the glands have undergone enlargement and show an increase in the number of cells The ducts are enlarged and lined by several layers of epithelial cells True intraductal papıllations are present, and visible grossly The presence of patches of multiple cysts and focal scarring scattered indiscriminately throughout the breast, and often in the opposite breast, does not exclude the possibility that more serious lesions may be present Careful search must be made for small, firm zones of induration in the tissue between the more innocuous cysts The differentiation of the benign forms of intraductal and intracystic papillary tumors from the malignant depends on the nature of the epithelial cells The benign pattern of uniformity, regularity, lack of cellular atypism and the appearance of secretory function in these cells aids in distinguishing the benign lesions from those malignant forms which are still limited to the duct or cyst (Figs 2 and 3) The pattern of lobular carcinoma in situ often does not have many features which permits it to be diagnosed with certainty when compared to a florid form of sclerosing adenomatosis The glandular lobules of carcinoma in situ are ·15 Pathologic Classification of Breast Tumors Fic 3.- Intraductal carcinoma This metastasizing peoplasm is still limited to a cluster of enlarged The cells fill tho ducts in a cribriform amngement Approd mately 175 X enlarged and packed with colls which may be uniform in appearance (Fig 4) There is a proliferation of tho cpithelium of the terminal ductules into the lobules without invasion of the strom On frozen section examination these non invasive lesions poso a difficut problem and care must be taken not to confuse them with forms of sclerosing ndenomatosis, as well as other benigo conditions such as hyperplastic apocino glands The microscopic pattern of carcinoma of the breast rarely shows a pure form, such as a typical adenocarcinoma. Alore commonly it is mied, and mcludes combinations of scirrhous papillary and medullary patterns, together with somo distinctly mucold or colloid types Gading of these tumors may be difficult in as much as the degree of differentiation will vary according to the pattern in tho arca under armontion The closer the tumor resembles a well-differentiated Adenocarcinoma, the cast it is to grade The relatively undifferentiated mixed scirlious and medullary tumors are usually classified grades III and IV Carcinoma of the breast gres rise to metastases by way of direct extension inAltration of lymphatics, or through the blood stream There is a greater ten clency for lesions in the lateral hemisphere to metastastze to the axillary lymph

·the skin It is more common in the large pendulous breast, and very infrequent
2
1
1
nodes, the medial lesions will more frequently involve the internal mammary
dissection to avoid cutting through tumor-containing lymphatic pathways Distant
metastases involve any organ or system, but there is a predilection for either the
to the endocrine system, particularly adrenals, ovaries, and hypophysis frequently
The combination is never excluded Metastases
Involvement of the liver by extensive metastases has serious clinical
significance in that the impairment of liver function, particularly of hormone
metabolism, may affect the tumor by increasing its rate of growth
breast involved by tumor with concomitant inflammatory change is usually
known as the primary type When the inflammatory signs appear in a breast
which already contains a carcinoma, it is listed as the secondary type The
inflammatory appearance is due to spread of the tumor into the lymphatics of
16 Pathologic Classification of Breast Tumors
FIG 4 Lobular carcinoma in situ
The lobule is greatly enlarged and the usual cells
are replaced by packed sheets of polyhedral cells contained by an intact basement men
brane Approximately 450 X
chain of nodes The lymphatic extension to the regional lymph nodes 19
to take place as a solid plug of cells in the lymphatics, thus requiring
5
thought
block
skeletal system or the viscera
Occur,
classified as inflammatory carcinoma
When both occur simultaneously it is

·Pathologic Classification of Breast Tumors 17 Fic 5-Sarcomatous appearance of stroma of cystosarcoma phyllodes chancterized by multinucleated giant cells and spindle cells Approsmetoly 100 X in the senile breast Whenever encountered it significs an extremely malignant condition with very poor prognosis The malignant forms of breast tumors are manifold (Fig 5) yet most adhere to a fired pattern of growth and spread. It is also very difficult to determine prognosis from tho microscopic sections alone. For these reasons once diagnosis has been established other criteria relating to the entire picture of the particular tumor in the patient at hand are necessary to determine proper care and treat ment These important considerations forin the basis of the discussions which follow 2 ·Chapter 3 BENIGN TUMORS OF THE BREAST Few conditions cause as much anxiety and worry to the patient as do tumors of the breast The reasons are not simple or clear The breast is, of course, the most superficially placed of all organs where cancer frequently occurs, but there are deep psychogenic reasons which make the thought of loss of the breast terrifying to the average woman Five years ago, in our personal practice, we operated on as many cancers of the breast as we did on benign lesions of the breast.10 For the past three years, our operative records show twice as many benign tumors as cancers In addition, the number of breast conditions seen and not operated on now almost equals the number in which there was surgical intervention Similar facts have been reported by McSwain 7,8 The number of malignant and benign tumors of the breast removed at Vanderbilt University Hospital during the period 1925 through 1945 in comparison with those excised from 1946 through 1949 showed that in the earlier period there were more malignant tumors (352 or 51 per cent) than benign tumors of all types (337 or 49 per cent) In the later period only onethird (114) of the tumors were malignant, two-thirds were benign (231) The reason for this changed incidence probably is due as much to the efforts of lay education as any supposed change in the nature of the disease itself 4 Patients are aware of the potential dangers of a breast lump and seek medical advice more readily This increases the overall number of breast tumors examined, the majority of which are benign One might say that we are now getting a better cross-sectional index of the general population From the physician's point of view a major problem in dealing with tumors of the breast is accuracy in diagnosis Unfortunately, this usually means tumor removal and microscopic examination which subjects the patient to the physical and mental trauma of surgery No matter how minor such a No matter how minor such a procedure may be few operations are attended by more worry and near hysteria Nevertheless, as Riddellº has said, “We must grow more and more accustomed to suspecting malignant disease on less and less clinical evidence” Cancer can only be diagnosed microscopically, and most often presents as a localized lump in the breast similar in many ways to the benign tumors Since part of the problem of breast cancer is the separation of benign from malignant tumors the importance of the former group is obvious Visi ·Benign Tumors of the Breast 10 CHRONIC CYSTIC MASTITIS This is a disease of all the mammary tissue but in the majority of lastances its chnical picture is localized to a specific area of the breast díost patients will complain of a lump mass or pain in the upper outer quadrant of one braust though the process is undoubtedly bilateral Clincally one may describe three brcal groups of patients with this disease The first group which may be separated includes young women, usually between eighteen and thirty years of age who complain merely of pain in the breast nnd on examination exhibit tender fir diffusely thichcned areas most commonly found in the upper outer quadrant These have been alled painful breasts, mastodynia or mazoplasia all terms which indiante a mild condition. Pain may be fairly intense during the premenstrual phase and is often marhedly relieved with the socond day of menses A diffuse lumpiness m the Premenstrual phase aften subsides dramatically with the menstrual flor These patients are often thin, intense emotional women who are greatly worried that the pain may signify cancer In occasional instances the pun may be severe However when reassured that such pain is commonplace m young women, and that the majority of cancers are "painless, most patients require no further therapy Associated gynecologic disorders are seen with this group fibromyomas, memorrhagia or scanty menses, and cervical polyps In addition to thyroid nodules There also will bo a history of difficulty in becoming pregnant Hormono therapy is contra indicated, and usually enhances the problem rather than resolves it sep 27) If this condition is due to an abnormal or unbalanced endocrine system caused by excessive estrogen stimulation during the period of maximum ovanan function, certainly the addition of estrinsic hormones seves further to increase this im balance. Whatever the true cause the clinical response to hormono administra ton, androgenic, estrogenic or otherwise has been disappointing Tho second and largest group and the one wheroin so much confusion exists, is probably a more exaggerated or later form of the mastodynias This condition is called variously Schimmelbuschs discase, benign parenchymatous hyperplası, ndeposls, adenocystic disease and a variety of other names Theso women ofton remain childless, are to their late thirties or early forties premenopausal have irregular menses and are nervous and inderweight. They often have small, dense mucer-edged breasts with multiple nodules on puupation Numerous small and Inrge cysts aro frequently palpated and on aspiration yield a murky, dark grew thin fuld or a clear strax colored fluid which is not sungwneous. Cytologic studies of the fluid does not show malignant colls Because of a higher and advancing age group these patients require more aggressive treatment, primarily almed at ruling out aineet The Dodularity and thickening are more localized and tumor the Pain and tenderness are not so prominent and changes with the menses not to marked, the process tending to remain constant so that thic clinician ·20 Benign Tumors of the Breast finds it difficult to make a diagnosis Overlying skin dimpling may occur and is seen in about 10 per cent of the patients. This is especially so when breast tissue changes are about the areola margin If the disease has been of any duration, with noticeable breast changes of engorgement and resolution, axıllary lymph nodes become enlarged which further complicates the picture The majority of excisional biopsies performed are in this group. Once the diagnosis of cancer has been ruled out routine follow-up examinations at threeto six-month intervals is all that is necessary. Fibrocystic mastitis is probably a self-limiting disease which tends to disappear or resolve after the time of the menopause Since most of the patients in this group are premenopausal the process may be expected to control itself with time The third group are those patients with solitary cysts This lesion was fully described by Bloodgood2,3 and the term blue-domed cyst popularized These patients are older, postmenopausal and frequently show a large amount of fatty infiltration in the breast tissue The breasts on examination are soft and full without nodularity or thickening The cyst usually arises suddenly with some associated pain They usually are discrete, single and tense, occasionally multiple, and unassociated with other systemic or generalized disease The cysts are filled with thin, turbid, yellow or greenish fluid Diagnosis of the cyst is not difficult It exhibits the classical slippery, freely movable characteristic as if the tumor is trying to elude the examınıng finger When “cornered" and pressed slightly it feels tense and “gives” a little, eliciting slight or moderate pain At times it may be very hard, especially if surrounded by a zone of mastitis, and simulate a solid tumor Rarely is there any skin attachment Although aspiration of any breast tumor without obtaining a definitive diagnosis is risky, aspiration of breast cysts is a commonly accepted and approved method of management On aspiration one may get 5 to 10 cc of turbid yellow or greenish fluid, often under pressure Usually, this is all the treatment that is necessary, and after two or three weeks the breast tissue feels smooth and normal at the site of the aspiration If small localized areas of residual induration persist beyond two or three weeks it is best to perform an excisional biopsy Aspiration of a simple cyst is a safe procedure provided the patients are carefully selected and both physician and patient are prepared for excision of any residual localized or indurated mass that does not subside after a few weeks It is not suggested by this that all cysts should be treated first by aspiration, but merely that when the diagnosis is highly suggestive this is one method of treatment which may prevent the necessity of a more major operative procedure in the form of an excisional biopsy It should be apparent that not all patients with fibrocystic mastitis can exactly fit into these three broad groups Many patients will have signs and symptoms which correspond to all three groups, young women may have solitary cysts and older women mastodynia alone Grouping all of these patients together, and disregarding their clinical classıſı- ·Bonign Tumors of the Breast 21 cation the patient that is most commonly seen with chronic cystic mastitis will bo between forty and forty nine years of age complain of pain in the upper outer quadrant of one breast, and point to a lump which is slightly tender on palpation and which was the cuse of her secking medical advice She will have waited about two to four weeks before consulting her doctor On examination a slightly tender diffuse nodulant will be felt, most marked in tho upper outer qundrant. There will be a poorly outlined, thickened, irregular mass which In some patients appears to be composed of multiple small cysts and large, thickened, cord like lobules On palpation these tumefactions will seem to be part of the brenst tissue itself and will not move freely Very occasionally thero may be skin retruction with slight pulling of the nipple Because of its somewhat vaguo nature and because of a still relatively obscure etiology specific treatment is lacking Because chronic cystic mastitis is a disoase of all tho mammary tissuo it is obvious that local excision is not curative Surgery is performed primarily to rule out cancer Statistical evidence which shows an increased (3 to 5 per cont) liability to for cancer in these patients (SCCP 31) is a secondary consideration. Surgical Technique of Excisional Biopsy The patient is placed supine on the table with one or both arms extended at right angles on an am board (Plato 1) The art board and table mattress are of equal height so that no injury occurs to the arm at the edge of the mattress The arm on the side of the involved breast is held in slight pronation, thumb up so as not to stretch the axillary nerves and musculature It is draped frco. The opposite arm is used for intravenous medication and may be draped to the side if desired General anesthesia is used A low other screen shields the head and nech arca from the opemtive field Fino absorbable sutures are used for all biopsy and other smaller operations on the breast. In most instances a radial incision in the direction of the duct system is made (Plato 2) Where skin dimpling is presont an eliptical incision which cncome passer the dimpled area is used (Plate 2) Círcumareolar incisions are made for papillomas and snus tracts as the extent of resection required is less in these cases (Plates B and b) Incisions are placed so that they can be completely encompassed by those made for a mdical mastectomy should the latter bo nec essary The use of frozen section analysis and immediate ndial operation is done routinel All patients are prepared for this by franh discussion preoperatively The deeper tissues aro Incised, and small flaps developed by undermining on each sido (Plate 3) By grasping the area with a towel clip in the region of the tumor a large block of tissuio is pulled upward and dissected free (Plate 4) This is an optional maneuver Because there is some chance of piercing tho tumor with the prongs of the clip thereby spreading malignant cells, dissection of a gC7ICTOUS block of tissue surrounding the tumor an be performed without

·22
Benign Tumors of the Breast
PLATE 1
D
PLATE 2
r

·Benign Tumors of the Breast
23
PLATE 3
PLATE 4

·24
Benign Tumors of the Breast
PLATE 5
de
Ronally
a)
ot
PLATE 6
(

·Benign Tumors of the Broad
22
PLATE 7
PLATE 8
f

·26 Benign Tumors of the Breast retraction of this type The specimen is dissected off the underlying pectoralis major muscle (Plate 4) so that one dissects beneath the involved area and removes all necessary tissue. A frozen section is performed immediately If the tumor is benign the wound is closed in layers (Plate 5) using fine vertical mattress sutures of silk on the skin. A small, soft rubber drain is placed at one end (Plate 6) and is removed the following day. When the tumor removed is malignant, hemostasis is secured as usual, and the wound packed with a dry gauze pad (Plate 7) (Plate 7) The skin is tightly sewn with a running, imbricating suture of silk which turns in the edges (Plate 8). The patient is then is then re-prepared, and re-draped, new instruments used, gowns and gloves changed and an immediate radical mastectomy performed BIBLIOGRAPHY 1 BISKIND, M S, BISKIND, G R and BISKIND, L H Nutritional Deficiency in Etiology Mastitis, Surg, Gynec, & Obst, 78, 49, 1944 2 BLOODGOOD, ) C The Blue-Domed Cyst in Chronic Cystic Mastitis, JAMA, 93, 1056, 1929 3 Chronic Cystic Mastitis and Blue-Domed Cysts, Arch Surg , 3, 445, 1921 4 Cancer of Breast at Mayo Clinic Procedings of the Mayo Clinic, 32, 645, Nov 13, 1957 5 HENDRICK, JAMES Results Treatment Breast Cancer, Ann Surg, 146, 728, 1957 6 POLLACK, RS Tumors of Breast, Amer Prac, 3, 393, 1952. 7 McSWAIN, B BARTON, and COLES, J H Tumors of the Breast, Cancer, 10, 1957 8 McSWAIN, B and YARBOROUGH, ) Breast Tumors, J Tennessee M A, 43, 441, 1950 9 RIDDELL, V Early Diagnosis and Treatment of Carcinoma of Breast, But M J. 2, 635, 1948 10 SALTZSTEIN, H C and POLLACK, RS Benign Tumors of the Breast, JAMA, 140, 997, 1949 ·Bonign Tumors of the Breast 27 MIEDICAL TREATMENT OF CHRONIC CYSTIC VLASTITIS The growth and development of the ducts, glands and stroma of the breast, with the formation of a specific glandular pattern is under the influence of substances elaborated by the endocrine system Tho dramatic histologic and functional changes 10 pregnancy and lactation are related to the level of specific hormoner in the body The less obvious changes that often taho place in the monstrual cycle are also the effect of horional stimulation and probably the result either directly or indirectly of changes in the estrogen androgen balance The origin of these latter hormones in the ovary and the adrenal cortes, and the possible transformation from one steroid typo to another is slowly being clarifed In addition, the role of related hormones and chemicals in foodstuffs are often overlooked as factors that influence the lovel of those substances in the body The organ in the body that regulates the level of most of the endogenous as well as the exogenous bormones, is the liver It contains the enzyme systems capable not only of transforming steroids of one type to another but also of metabolizing certain ones to an inactive state 1 In animal experiments it has been shown that the latter function is influenced greatly by the nutritional status, and that a major fnctor controlling the latter is the vitamin B complex as well as the protein content of the diet. In the animal deprived of vitamin B complex the liver no longer inactivatos estrogen, but it continues to nactivate testosto rone.*.* This leads to an alteration of the estrogen-androgen pattern in the body with the appearance of the so-called hyper-estrogen syndrome * Patients with the hyper-estrogen syndrome have one or more of the following signs and symptoms premenstrual tension, cyclic mastalgia, cyclic focal breast hypertrophy lower abdominal bloating, menorrhagia, metrorrhagia, the feeling of impending menstruation and other related symptoms. The improvement of Ilver function with control of estrogen metabolism gencrlly relieves most of these conditions within several months lo many instances there may be undue target organ sensitivity lunited just to the breasts so that they may undergo soverc change in the premenstrual period with distinct lumpmess On the other hand, the process may be limited to just a lobe of one breast, and the engorgement and fulness may not occur at each period but at random periods The swelling may or may not regrets completely between periods Estrogen stimulation of the breast causes enlargement of the glandular lobules with an increase in associated connective tissue Over a period of time with alternating stimulation and regression the amount of connective tissue may slonili increase with a variable component of active glandular tissue Cysts will form, and a low grade inflammatory infiltrate is often superimposed In somo patients a single poorly defined nodule may become demarcated from the re mainder of the breast parenchyma, in others, there may be multiple zones of palpable difference in each breast. The former condition is difficult to differen ·28 Benign Tumors of the Breast tiate from an early carcinoma and if the examiner cannot be certain a biopsy is indicated Multiple masses are much more likely to be a hyperplastic process, but the possibility that one of them may be neoplastic should never be overlooked These patients, if examined carefully, will have clinical evidence of nutritional deficiency Palmar erythema is an outstanding sign Many show cutaneous vascular spiders as well as easy “brusability” Changes in the tongue and lips are frequently noted The former may vary from thickening with loss of the fine granular mucosal papıllations, to a flattened, atrophic, smooth tongue The corners of the mouth frequently show a crack which heals with difficulty Total body weight is rarely an index of the nutritional status of the patient, except in those rare instances when starvation is being carried out deliberately Liver function tests occasionally show slight impairment, particularly while the patient is in the mid-portion and second half of the menstrual cycle Treatment of the liver to correct a hyper-estrogen syndrome, with particular emphasis on the nodular changes found in the breast, requires complete therapy over a protracted period " It is not always entirely successful, but deserves therapeutic trial Complete therapy means the administration of all of the presently known crystalline B vitamins, as well as an oral, whole crude liver preparation, and an increased protein intake in the diet In some instances yeast, yeast extracts oi rice bran extracts may be substituted for the crude liver extract or whole liver Up to the present time, no one single factor in the vitamin B complex or in the crude liver brings about complete return of normal liver function and relief of the clinical picture It has also been found that unless all synthetic vitamins and crude liver are supported and supplemented by an incieased total protem intake in the diet, there will not be a satisfactory therapeutic result The most effective preparation of liver is a desiccated, unfractionated powder This is taken orally in an amount equivalent to 40 gm of whole liver The synthetic vitamins include 36 to 45 mg thiamine, 21 to 36 mg riboflavin, 12 to 27 mg calcium pantothenate, 200 mg niacinamide, 3 mg pyridoxine, 210 mg choline, 27 to 150 mg inositol, 5 to 10 mg folic acid and 25 mcg vitamin B12 The liver and vitamin supplements are divided and given in 3 daily doses after meals In some instances, where gastrointestinal absorption is impaired due to longstanding nutritional deficiencies, parenteral therapy may be required and preparations containing thiamine, riboflavin, niacinamide, pyridoxine, calcium pantothenate and vitamin B12 are given intramuscularly in addition to the above. Injectionable liver extracts which contain only those factors soluble in water have been found to be ineffective and cannot be substituted for the oral preparations It frequently will be necessary for patients to limit their total fat intake as they commonly have a tremendous stimulation of appetite on this regimen To prevent weight gain they are cautioned to limit fat and carbohydrate intake rather than protein intake A daily diet which includes at least 2 grams per kilogram body weight of protein and approumately 1 gram per kilogram of fat, with the remaining caloric intake made up of carbohydrate, will provide the ininimum requirements ·Benign Tumors of the Breast 20 One of the first indications of the effectiveness of thus therapeutic regimen is noted in women who are still menstruating They will state that the onset of menstruation 'ame without warning and the customary abdominal bloatfog and premenstrual tension often disappear within a month of treatment. The c clic mastalgia also dimmishes in about that time and within two or thrce months is hardly noticeablo The menstrual flors diminishes, and the number of dnys of fou decreases. In the older age groups where there has been some obesity there is a change in the configurntion of the body with loss of fat around the hips, on the back of the deck and between the shoulders. The complexion becomes less muddy with less sebaceous secretion from the glands of the faco particularly around the nose Within two or three months bilateral diffuse lumpiness of the breast often disappears and painful podules regress Occasionally lesions which contain cysts decreaso in size, and somotimes the withdrawal of Auld from these cysts permits them to collapse and slowly be obliterated In some instancas however a zone of thickening will remain and if there is any doubt concerning tho nature of this Icston, it should be explored and removed Lesions of this type which have been removed and examined have always been composed of compact fibrous tissue in which there are a fet atrophic ducts and snall breast lobules It is necessary to maintain the patient on the nutritional regimen for long perlods With com pleto regression of the nodularity of the breast, the intako of crude liver and synthetic vitamins may be halved Studies have shown's that if treatment is terminated, recrudescence of the lesſons frequently takes place Subsequently thomane therapy may not be quite as offective This method of treatment is not a panacea nor is it intended to replace surgical blopsy whon indicated. After biopsy has been performed and the diagnosis nccumtely established, it may be worthwhile to proceed with n course of medical therapy as outlined. Its greatest usefulness seems to be in young women whose chief complaints are mastalgia, and other early signs and symptoms of the mastitis syndrome (sce p 18) It is lacking when the disease process is advanced or Irreversible, which is the more dangerous dinical form and the stage when biopsy is more imperative BBLIOGRAPHY 1 BLSKIND, GR and WLANE, ) The Inactivation of Testosterone Propionate and Estrono in Rats, Bull Johas Hopkins Hosp 65 212, 1939 2 BESKIND MS and BESKIND GR Effect of Vitamin B Complar Deficiency on Inactivation of Estrono in the Liver Endocrinology 31 109 1942. - Inactivation of Testosterone Propionato in the Liver During Vitamíı B Com ples Deficiency Alteration of the Estrogen-Androgen Equilibrium, Endocrinol og 29 97 1513 + BUIND MS. BISIIND GR. and BESKIND LH Nutntional Deficiency in the Etiology of Victorrhagia Vetrorhagia, Cystic Vlastitis and Premierstrual Tension, 11 Further Observations on Treatment with the Vitamin B Comples Surg Gyrict & Obst 78 49 1944 3 BISOXD V1 S Nutritional Therapy of Endocrino Disturbances Vitamins and Hormones, ll. lei lork, Acaderalc Press Inc 1916 3 ·30 Benign Tumors of the Breast CHRONIC CYSTIC MASTITIS AND CANCER The relationship of chronic cystic mastitis to cancer has varied widely among different investigators Ackerman and del Regato? stated that it is "directly proportional to the liberality of the pathologist in diagnosing such a lesion" Foote and Stewartó similarly have stated that “the concomitant occurrence of cancer in so-called chronic cystic mastitis will vary statistically according to the selection of lesions By and large, pathologists have agreed that the microscopic changes of small cyst formation and proliferation of the epithelium occur in a large percentage of cases of cancer of the breast MacCarty and Mensings found 100 per cent of 967 carcinomas of the breast associated with chronic cystic mastitis Ewing reported at least 50 per cent, Semb,' 80 per cent Cheatle’ repeatedly emphasized the association of cancer and chronic changes in the breast Pathologists have differed with regard to the direct etiologic relationship of these changes to carcinoma Ewing and Warren10 both used the term precancerous and thought that epithelial hyperplasia preceded cancer in enough instances to be significant However, Foote and Stewart, after an exceedingly careful and critical analysis of 200 cancerous and 300 noncancerous breasts, found that the changes described in chronic cystic mastitis are just as common in noncancerous as in cancerous breasts They further state that it has not been proved that these changes are the focal starting points for cancers of the breast in any sufficient number to be significant This appears to be the conclusion of more recent reports Hendricko operated on 484 patients with cystic disease of the breast and made follow up examinations on 91 per cent He states the incidence of carcinoma was no greater in this group of patients than in the general female population Such a conclusion is also the experience of the author who in a ten-year study of clinic and private patients can determine no greater incidence of cancer in patients with a chronic cystic mastitis syndrome Confusion exists over the criteria which different pathologists use to diagnose chronic cystic mastitis In Foote and Stewart's material 59 per cent of the patients with cancer of the breast exhibited one of five cystic and proliferative lesions, cysts, papillomatosis of the duct, blunt duct adenosis, sclerosing adenosis and apocrine epithelium Sixty-five per cent of 200 noncancerous brcasts likewise contained one of these five features When two or three of the foregoing features were tabulated in the two groups, the difference between the cancerous and the noncancerous breasts was not outstanding, and the etiologic relationship of chronic cystic mastitis to cancer was not proved As the foregoing statements would indicate, there has been a steady tendency 10 regard these lesions as not necessarily leading to cancer Bloodgood, then White," Lewis and Geschickterand, more recently, Foote and Stewart," to inention a feu authors the realization has grown that present Starting with ·Bonign Tumors of the Breast 31 Information is not conclusive enough to state with exactness the precancerous nature of this lesion Unfortunately and despite the weight of evidence to the contrary the prac tidng physician is under considerable pressure to treat occasional advanced cases of this disease in a near mdical manner that is, by simple breast amputation. Most surgeons of experlence see a frequent association between advanced mastitis and breast cancer in the operating room Confronted with a previous mastitis history and a fully developed histologic mastits in the breast it is under standable why the surgcon may feel the disease is "pre-cancerous Although anatomic and scientific studies deny the existence of any pre-cancerous condition the conscientious, practicing surgeon, on the basis of what he sees in the operating room mny with some justification treat this disease by removal of all breast tissue uollateral or bilateral. Not that this is a recommended procedure it is not but it emphasizes the fact that there is a disparlty between two groups the clinicians and the pathologists Lending some support to the clinical group are the studies of Warrenº who in a careful and extensive clinical study followed 1,206 patients with chronic cystic mastitis Cancer developed in 42, or about 3 times tho incidenco expected in the normal population More concretely between the ages of thirty and forty nine women with chronic mastitis havo 117 tmos greater incidence of cancer After Afty years of age the incidence is 2.5 times greater It is still believed, therefore despito the lack of anatomic ovidenco that the prolifemtive lesions of chronic cystic mastitis predispose toward a slightly higher incidence of cancer Recommended treatment, nevertheless, is excisional biopsy of the area in question Close follow up examinations are necessary It is felt that if carct noma docs develop it can be detected in an early stuge and prompt treatment administered BIBLIOGRAPHY 1 ACKENSLAN LV, and deL REGATO JA Cancer Diagnosis Treatment and Prognool St. Louis, C Morby Co p 928 1947 2 BLOODGOOD J C. Pathology of Chronto Cystic Mastitis of Female Breast with Special Consideration of Blue Domed Cyst, Arch. Surg 3 445 1921 The Blue-Doned Cyst in Chronic Cystic Mestitis JAM.A., 33 1056 1929 3 CHEATIE, G L and LUDFOR, RJ Some Aspects of Rodium Treatmont of Carci noma with Cystological Reports of Some Cases, Practitioner 125 498 1930 CHICATLI, GL Lecture m Treatment of Vamman Carcinoma by Radia Hon, Brit. 11 J. 1 807 1830 Precancerous Conditions of the Broast, Cancer Roy. 5 81 1930 CHEATLE G I. And CUTLER, M Tumours of the Breast London, Edward Arnold & Co 1931 4 EWNO J E Neoplastic Discase 3 ed. Philadelphia W B Saunders Con p 532, 1928 5 FOOTT, F and STVART F Comparative Studies of Cancerous Venus Non- Cancerous Breasts Ann Surg 121 6 and 197 1945 6 HENDRICK, JASIES Results Treatment Breast Cancer Ann Surg 148 728 1957 ·32 Benign Tumors of the Breast 7 LEWIS, D, and GESCHICKTER, C F Relation of Chronic Cystic Mastitis to Carcinoma of Breast, Surg , Gynec & Obst, 66, 300, 1938 8 MACCARTY, WC, and MENSING, E H The Relationship Between Chronic Mastitis and Carcinoma of the Breast, in MELLISH, MH Collected Papers of the Mayo Clinic, Philadelphia, W B. Saunders Co, 7, 918, 1915 9 SENIB, C Fibro-Adenomatosis Cystica Mammae, Acta path et Microbiol Scandinav (Supp) 5, 62, 1928, Pathologico-Anatomical and Clinical Investigations of Fibro-Adenomatosis Cystica Mammae and Its Relation to Other Pathological Conditions in Mamma, Especially Cancer, Acta chir Scandmav (Supp 10) 64, 1, 1928 10 WARREN, S The Relation of "Chronic Mastitis” to Carcmoma of the Breast, Surg, Gynec & Obst, 71, 257, 1940, Prognosis of Benign Lesions of Female Breast, Surgery, 19, 32, 1946 11 WHITE, WC Cancer of the Breast, New York, Harper & Brothers, p 40, 1930 ·Benign Tumors of the Breast 3.3 1 PAPILLOVAS OF THE DUCT What to do with the patient who exhibits occasional bleeding from the nipple in the absence of a palpable tumor is still a perplexing problem and much disit greernent ersts on the extent of surgery necessary to treat this condition properly In studying total hospital experience seveml authors have found that about 50 per cent of the patients who have bleeding from the nipplo also have breast cancer 1 10 16 However in other more recent articles to the reported incidence of crunoma associated with nipplo discharge is far less All degrees of incidence from 5 to 70 per cent have been reported. There is a difference, too regarding the incidence of cancer in those breasts with or without a palpable tumor The problem for the practicmg surgeon is naturally greater in that group of patients where no tumor is felt In the palpable group biopsy is promptly performed and tho question settled. It would appear both on the basis of personal experience and the litera turel,4,8 11,18 that the inddonce of cancer in the breast in those patients showing nipple discharge but no palpablo tumor is very low probably 1 to 2 per cent or less. Troves, 17 in a study of all arcinomas of the brenst found 2 per cent of 1000 cases who had bleeding from the nipple as their first symptom It is also felt that the truly sanguineous discharge may possibly be more important regarding cancer than the non bloody sorows or turbid typo which is more common and seems to be even less significant clunially However Axelrod takes issue with this Fleming and Drosd: found bloody discharge only in breasts having papil lomas Bloodgood' felt that discharge, either blooly or serous usually indicated an intraductal papilloma. Nevertheless, many consider bleeding from the mupple a grave symptom, certainly the patient does and in the past breast amputation had been frequently recommended The vast majority of patients however who have bleeding from the nipple do not have cancer and a conservative method of treatment may be carried out with safety This is especially true when bleeding occurs in the absence of a palpable tumor La general, one might discuss four types of bleeding from the nipple First, bleeding may occur with a large hard, palpable mass that clinically resembles cancer Second, the bleeding may be associated with a mass that is more char acteristic of chronic mastitis Third, the bleeding may come from a small palpable tumor usually in the periphery of the areolar region, which contains a papilloma such an nrea often transillummatos darkly because of contained blood and the tumor is easily localized by palpation. The fourth type, which frequently presents diagnostic difficulty and is of chief concern, is slight bleeding from the nipple in the absence of a palpable tumor Such patients may complain of bleeding for only two or three days during the vear occasionally occurring after slight trauma on examination. Pressure at one point about the periphery of the nipple 3 ·31 Benign Tumors of the Breast usually produces bleeding, but the localization of the tumor is not always easy or accurate, since in many of these cases bleeding may be produced with pressure over half of the areolar circumference or over a large portion of the breast Furthermore, significant information is not always obtained in these patients by transıllumination Because of the difficulty in localizing this group of tumors, amputation of the breast, rather than local excision, is frequently recommended When the excised tumor is examined microscopically, it proves in most instances to be a small duct papilloma, entirely benign Another indication frequently cited for mastectomy is the multiple nature of these papillomas By roentgenographic studies of the breast after the injection of a radiopaque oil into the nipple ducts, Hicken" found that in many instances papillomas involved all of the mammary tissue Foote and Stewart studied generalized duct papillomatosis, among several other histological features, in 300 cancerous and 200 noncancerous breasts Using as their criterion “all stalked papıllary adenomas, usually macroscopic,” in the large or medium sized ducts, they found that the incidence of papillomatosis was approvamately the same in cancerous (36 per cent) as in noncancerous (29 per cent) breasts In the age group between forty and fifty years, the frequency was identical in the two series (40 per cent) As a matter of fact, these investigators found that macroscopic papillomas were more characterisic of benign rather than of cancerous breasts, and the multiplicity of the lesions showed no significant difference in the two groups They concluded that “Although it is rare to find any early duct cancer of the breast in the absence of a typical papillomatosis, the actual number of papıllary lesions that eventually become mammary cancers must necessarily be a very minute fraction, and we know of no way to prognosticate the probable course of any given histologic type” Despite these reassuring opinions regarding the nature of the lesions causing nipple discharge it has long been known that any bleeding from the nipple should be carefully investigated and its exact cause established Any intraductal papılloma of the breast should be excised surgically even though the bleeding or discharge may have ceased, for such a tumor may continue to grow even in the absence of symptoms When an intraductal papilloma is removed, and subjected to histologic examination it is usually always benign and shows no infiltration beyond the duct epithelium (see Figs 2 and 3, pp 14 and 15) Therefore, treatment should be aimed merely at removing the palpable tumor In those instances where no tumor is felt but where pressure over a zone or arca yields nipple discharge one is justified in removing a wedge or block of tissue, usuall subareolar, from such a region and examine it pustologically for malignant change Where a palpable tumor is present removal of this alone is all that is necessary Some scars ago, in order to find the exact location of a non-palpable papillomat, Ilichen described a method of localızıng duct papillomas in which a contrast + 1 1 ·Benign Tumors of the Breast 35 medium (Thorotrast) was injected directly into a large terminal duct of the nipple. This diagnostic procedure luas not become popular in spite of the fact that Hicken stated that in more than 300 such eraminations he had encountered only three or four untoward reactions in the early part of his series. The method was criticized by Romano and McFetridgels who found granulomas necrosis and edemn in 4 of their 23 patients Furthermore, Sowers and Masson't reported a ause in which fat necrosis following the injection was of sufficient magnitudo to warrant mastectomy Such a refinement has become wholly unnecessary Tho areolar pressure test localizes a zone of Involved tissue and removal of this is more adequate thempy than carcfully dissecting out one main duct alone In those instances where a tumor is not palpable and the pressure test fails to localize the Involved zone the patient is instructed to leave the breast entirely at rest, and to wear a brassière continually After one week she is asked to return Frequently by that time the small ducts will have Alled with enough secretion to bo palpable and yield nipple discharge on pressure Should no discharge be elicited the patient is instructed to return at regular intervals until the exact area or zone is located. Local surgical excision is then performed Surgical Technique of Rescction of Duct Papillonnas The patient is placed supine as in Plate 1 A circuidareolar incision is made Just beyond the areolar margm (Plate 9a) and following one half of the arcum ference of the arcola In patients with a draining sinus tract a curved, elliptical incision is made which excises tho sinus opening (Plate 9b) The nipple and areola are dissected backwards by undermining, and the opposite edge also is relcised (Plate 10) The nipple and areola aro dissected back almost completely preserving about half of the nipple duct system The subareolar ducts and the Involved duct and papilloma can be visualized (Plates 10 and 12) A sagittal view is seen in Plato 11 A diamond shaped wedge of breast tissue is dissected freo (Plate 12) This is facilitated by grasping the area, not the tumor in a toivel dip and retracting it upwards The specimen is removed and submitted for frozen section analysis I benigo as is usually the case, the deep layers are closed (Plate 13) and the skin drawn together with fine vertical mattress sutures of silk (Plato 14) A small, soft rubber drain is placed at one end, and removed in 24 hours The amount of breast tissue removed, and the extent of the duct system resected, will depend entirely on the size of the tumor and the degree of breast tissue involvement. The exposure gained with this incision can, of course, be more limited with resection of only the fnvolved duct Because papillomatosis is a generalized process and the involved duct pot always clearly defined, this is rarely possible

·36
Benign Tumors of the Breast
PLATE 9
1
a
1

·Benign Tumors of the Breast
37
PLATE 10
Skin and fatty layer lifted
and freed from
breast fissue
1
44.
PLATE 11
Papilloma
in duct

·38
Benign Tumors of the Breast
PLATE 12
Nipple and areola,
undermined
Zone of breast tissue
to be resected
hin

·Benign Tumors of the Breast
30
PLATE 13
Closing deep layer
PLATE 14
Skin closure with small
soft drain

·10 Benign Tumors of the Breast BIBLIOGRAPHY 1. ADAIR, 1.E. Sangumcous Discharge liom the Nipple and Its Significance in Relation to Cancer of the Breast A Study Based on 108 Cases, Am Surg, 91, 197, 1930. 2. AVINOI), II Nipple Discharge, Am. J. Surg , 87, 247, 1954 3. BLOODGOOI), J. C.. Changmg Picime of Lesions of Brcast, Am J. MSc, 179, 27, 1930. 4. CAN!!!! LL, O. J.. Thc Blocdmg Nipple, Surgcry, 19, 40, 1946 5. I'I MING, R. M, and Drosi), R. E Lesions of the Breast, South M J, 47, 922, 1954. 0. j'0011., , and Sirwani, F. Canceious Versus Non-Cancerous Breasts, Ann Smg, 121, 6, and 197, 1945. 7. Ilican, N. Y., Besi, RR, HUNT, H. B, and HARRIS, T T Rocntgen Visual iration of Breast Lesions, Am. 1. Roentgenol, 39, 321, 1938 8. K11.com, A.R, HLEMING, R., and Ramos, M M Cance With Nipple Discharge, Sung, Gynec, und Obst, 96, 649, 1953 O MADALIN, 11. E., Clarim7, 0. T, McDoxılı), J. R. Discharge From the Nipple, Ann Sug, 116, 75), 1957 10. Mm21, E. M., and LLWIS, D., The Significance of a Serohemorrhagic or Hemoralagic Discharge liom the Nipple, JAMA, 81, 1651, 1923 11. Mill, E W Lesions of Bicast, S Clm No Amcı, 757, 1924 12 ROATANO, S. A., and McFNGI, E. M. The Limitations and Dangers of Mammography by Contrast Mediums, LAMA, 110, 1905, 1938 13. SALTZU IN, II, C., and POLLICK, R. S. Papillomas of the Breast, Cancer 1, 625, 1918 11 Sowis, B F., and MASSON ) C Mastitis Follow mg Use of Thorium Dioxide Proc Stair Meet, Mano Clm, 12, 529, 1937 15 Sioul, a P Pathology m Lesions of Breul, South A 1, 43 205, 1950 10. Sromuns, l. E The Significance of Bleedmg o Discharge From the Nipple, Sug, Gunes & Ohsl., 61, 537, 1935 17. THUS, N Bleeilmg Nipple, Ti. d Stud Coll. Plusicians Puladelphur, 1968, 19.11 ·Benign Tumors of the Breast 41 it per cent FIBROADENOMAS Tumors of this type liave several distinctive characteristics, hence diagnostic difficulties are considerably less than with chronic cystic mastitis or intraductal papillomas As with other kinds of mammary tumors the upper outer quadrant is the most common site In the majority of patients the first symptom is merely the presence of a lump in the breast Rarely will pain be associated with the tumos They are freely movable, well outlined and firm without tendemess Occasionally they may grow to large size. Not Infrequently there is a history of prolonged duration without appreciable change When asked why they let go patients usually answer "because it did not bother me." The majority of these tumors occur in females between the ages of twenty and thirty nine although patients over sixty and under tiventy may show such tumors In Geschickter s series 8 por cent were beyond tho menopause and in 10 tho tumors were present before the first menses In a study of 28 patients with this tumor 8 had associated gynecologic com plaints. Threo had fibromyomas of the uterus, one of them having a thyroid adonoma as well Three had menstrual irregularities and 2 were experiencing symptoms of the menopause The relation of this tumor to periods of estrogen stimulation has been commented on by several authors Fibroadenomas occur predominantly in women of the child bearing period The tumors are llable to rapid growth during pregnancy and also when they occur at the time of the menopause This is reron enough for early local excision In addition, malignant degenemtion is not vecommon Of 29 sarcomas of the breast collected by Geschickter 11 were thought to have formed from preexsting fibroadenomas Adair and Hermann' collected 30 sarcomas and believed that 4 were from previous fibroadenomas Cystosarcoma phyllodes (giant intra canalicular fibromyroma, giant mammary myxoma) 15 an old term denoting a large, slowly growing solitary tumor of the breast, considered to be benign. It is felt that these tumors also arise from preexisting Abroadenomas and may become malignant (sce section on cystosarcomas, p 42) which further emphn irzes the importance of exclsing a fibroadenoma. As with any other breast tumor arcision and histologic examination is the only way to assure certainty of diag nosis. Although these tumors are relatively easy to diagnose clinically in an occasional instance the tumor may be hard to differentiate from cancer without microscopic study BIBLIOGRAPHY I ADAIR, F, and HERRIAN J B Sarcoina of Breast, Surgery 19 55 1916 CESCHICITER, C F Discares of Breast Philadelphia, J B Lippincott Co p 380 1915 3 SALTZSTEIN HC and POLLACS, RS Benign Breast Tumors, JAM.A 140 997 1949

·42
Benign Tumors of the Breast
CYSTOSARCOMA PHYLLODES
Since 1838 when Johannes Mullers gave
the term cystosarcoma phyllodes to
a large, bulky mammary tumor, and described its peculiar gross and
microscopic
features, it has been known by at least 26 other appellations ranging from
“hydated tumor of the breasť"13 to “giant intracanalicular fibroadenomyxoma."10
During the past fifteen
yeais
this tumor has become more readily recognized as
a distinct entity In 1931 Lee and Pack" published an excellent and exhaustive
review of the literature on this tumoi They collected 105 cases and added 4
of their own
Since then others2,0,7 0,10,12 have shown much interest in the subject
and added additional cases to the literature It is quite evident that Mullers and
1
1
Pic
Patient with cystosarcoma phavilodes revealmg huge sa, merlying dilated
veins, but lack of shin mvolvement

·Benign Tumont of the Breast 43 other carly writers encountered much later stages of these peoplasms than nro now commonly seen The early reports mahe great note of the large bulky size of the tumor which could only have renched such proportions after long neglect (Fig 6) When in this stage it is quite diagnostic The majority of these tumors appear in women is the premenopausal age group but extremes of Aftecn and seventy nine years of age have been seen The tumor is fim and freely movable When it attains huge sizo numerous dilated volns may be seen coursing through the overlying skin It is pontender and unattached. If not very large it cannot be distinguished clinically from a tense cyst or Abroadenoma On palpation it has a rubbery firm feel with clear and distinct margins There often is a history of a preexisting tumor probably a fibroadenome, which suddenly became much larger Lactation frequently is Associated with the rapid increase in size Footc and Stewart' have recently pointed out that the tumor need not necessarily bo of large size and that small tumors present the course, intracanalicular protrusions and connective tissuio cellularity seen in the Inrge ones Grossly the tumor tends to fall apart because of the enormous clefts and polypoid masses (Fig 7) These are placed intracystically and referred to as 7 14 1 9 10 11 12 13 15 16 17 10'19 20 21 22 » 31 25 20171*** Fic 7-Grous appearance on cut section showing enormous clefts and polypold masser intracystically placed ·11 Benign Tumors of the Breast “papıllary elephantiasis "J These masses may fill the clefts so well that they simulate a solid tumor The tumor may be multilocular and the cysts often confluent due to rupture of the intervening septa A thin straw-colored fluid is found within each cyst but at times the secretion may be mucoid or gelatinous The stroma is usually myxomatous, loose and hemorrhagic and of a grayısh-white, glistening appearance Most of the tumors are well encapsulated, but some mav be covered by a thin transparent membrane The tumor is not invasive and does not destroy the surrounding breast tissue Muller,8 in ius original description, states that “the extraordinary forms which cystosarcoma phyllodes assumes, at once suggest the notion of its cancerous nature, and yet, the disease is perfectly innocent and as far removed from carcinoma as are those nonsuppurating cauliflower condylomata of the penis, and of the female genitals, which have so often been mistaken for cancerous structures” (See Fig 5). Recent reports2,11,12,14 however, have shown that all of these tumors cannot be considered “perfectly innocent A small percentage become very malignant with rapid and widespread metastases and death Each of these tumors is a potentially malignant growth and deserves prompt surgical extirpation It is best to refer to them as “benign” or “malignant" cystosarcoma phyllodes. In addition, if, as Lee and Pack" state, they arise from preexisting fibroadenomas the surgical removal of those very common and innocuous tumors takes on added importance It has been stated that the tumor often is present for a long period in a quiescent phase Sudden increase in size within a short space of time is frequently reported with the history of initial onset going back many years. This would appear to be true of the large, bulky lesions, but not so true of the smaller ones A personal study showed that over half of the patients with benign tumors had them for only one year, the majority for only six months A similar time sequence is seen with the malignant variety1º One may then look with some doubt on the theory of sarcomatous change of a preexisting tumor It may be just as probable that when malignant these tumors are so from their inception The malignant variant of cystosarcoma phyllodes is a very dangerous tumor Jetastases are widespread and dissemination is rapid because of its vascularity Spread, therefore, is usually by the blood stream Aullary become myolved but at that time blood borne metastases have also occurred Thus olservation is similar to that of others! -,112 although Cooper and Achermin. reported a case with ayıllary metastases and invasion of the underyling pectoralis 11ldjor muscle In treating the benign tumor complete local escision 1 adequate Il the tumor is huge this may require simple mastectomy Treatment of the maligunt variets is not so easily dismissed Because of its rapid invasion of the blood stream, and the fact that lymph node metastases probably occur after the has taken place simple mastectomy should be just as effective as radical master tom lymph nodes dio ·Benign Tumors of the Broast 45 In the occasional patient though, with axillary lymph node metastases or pectoral muscle mvolvement, and no other evidence of disease one would feel radical mastectomy indicated. Nevertheless, knowing the method of metastases, the frequent lach of lymph node involvement, the freedom from local invasion and the widespread dissemination one feels that the malignant variant of this tumor is one of the few indications for smoplo mastectomy BIBLIOGRAPHY I ADAIE, F E and HEHFULANN ) B Sarcoma of the Breast, Surgary 19 55 1946 2 COOPER, WG and ACIENSLAN L V Cystosarcoma Phyllodes Surg Gyn. & Obst., 77 279 1943. 3 FOOTE, F., and STEFANT F Quoted by TRETES 1 4 HILL, R P and STOUT A P Arch Surg., 4 723 1942 5 LOL, BJ, and Pac, GT Glant Intracanalicular Fibroadenomyxoma of Breast, Tho po-called Cystosarcoma Phyllodes of Johannes Muller An ) Cancer 15 2583 1931 Ann. Surg, 13 250 1931 6 MACIENZIE, K Hugo Fibroadenoma of the Breast Brit. J Surg 20 234 1835 7 MARCOWITZ, B and HOWELL, HL Rapid Growth of a Largo Breast Fibroma in a Young Girl, JAMA, 107 1013 1938 8 MULLER, ) Neber den Feinem Bau und dlo Formen der Krankhaften Geschwalste Berlin, G Reimer 1838 9 OWEN, F M and Adaus, WE Giant Intrucanalicular Fibroadenoma of tho Breast, Arch. Surg 43 588 1941 10 SMITH, I H Guant l'atracanalicular Fibroadenomyxoma of the Breast, Am J Surg 30 545 1935 11 STECILER, C and LANDALAN 11 Cystosarcoma Phyllodes with Metastarls Nov York State J Med 30 339 1950 12 TREVE, N Cystosarcoma Phyllodes of the Breast, Cancer 4 1286 1951 13 WARREN JC Surgical Observations on Tumours London, J Churchill, 1839 14. WIEJ W Malignant Vartant of Cystosarcoma Phylodes, Am J Cancer 40 458 1940 ·16 Benign Tumors of the Breast in size MISCELLANEOUS TUMORS Lipomas -Although lipomas are completely innocent tumors their presence alone may cause much worry and anxiety It may be difficult to be certain that they are only lipomas The majority occur in patients between forty and fifty years of age The tumors vary in duration, and some show progressive incrcase Most occur in the upper quadrants of the breast They are soft, superficial and frequently lie on top of the mammary tissue They are unattached, freely movable and, with few exceptions, nontender Occasionally some are firm, tender and attached to the skin The average size is 3 to 4 cm. Men are not infrequently involved If gynecomastia is excluded, lipomas are the most commonly observed benign tumors in the male breast Local e cision should be performed in each case Fat Necrosis -Recognition of this peculiar condition is important because of mimics carcinoma There is usually a history of injury, but occasionally the patient will have forgotten about the traumatic incident or not be able to recall it accurately A few days to a week later a lump will be noticed which may or may not be associated with an ecchymosis It may be nontender, and as observed will not increase in size but may become more firm On clamination onc feels a solid tumor, not freely movable and with a suggestion of induration Local excisional biopsy is the treatment of choice A clinical diagnosis of fat necrosis is naturally made easier in the presence of ecchymosis, yet one must also consider the coincidental finding of cancer in an area of injury Therefore, cven in these instances excisional biopsy would be best when a definite tumor persists more than a week or ten days Although the author fcels that trauma to the breast has no etiologic significance relating to the cause of cancer, one cannot avoid the medicolegal relationships involved When cancer is Coincidentally found nothing can shake the conviction from the patient's mind that it was caused by the injury clccessory Mammary Tissuc --Such tissue presenting in the extreme tal of the breast, near the avlla, may show a confusing picture Some patients huse bilateral masses in the tail of each breast Soreness and tenderness may bring their attention to this area On examination one finds soft, bulky, slightly thich. ened, poorlv outlined masses near the aulla One side may be more pronounced than the other As a rulc no treatment is necessary If i tumor is pulpated il should be removed for biopsy There is no evidence that tumors in this region ure any different or more frequently malignant than in other areas of the breast ·Chapter 4 GYNECOMASTIA IF THIS is a truly neoplastic condition it is probably the most common tumor seen in the male breast It is a benign lesion in which the male breast is enlarged, and often painful, and is seen in all age groups The peak age incz denco varies according to reported authors in Menville so series thirty-one to forty years of age in Larsers“ twenty-one to thirty in Jaaskelainen se also twenty-one to thirty and in Sitori and Veronesie fifty-one to staty In the authors experience it has been seen predommantly in the thirty to forty year-old group It is seldom seen before ago ten Secretion from the nipple, usually serous rarely anguineous, though commonly seen when the tumor is caused by hormone alteration, is not a prominent feature of gynecomastia occurring without evidence of other disease Two forns of the disease are described The first type occurs spontaneously without hormonal relationship the second occurs as a related finding incidental to disease in another part of tho body The latter type is more frequently bilateral and is seen in conditions where the normal endocrino balance has been altered. This situation would occur after the administration of estrogens for the treatment of prostate cancer in conjunction with liver disease with testicular lesions, primarily those causing atrophy or in hormone producing testicular tumors, and in chronic dobilitating systemic disease and malnutrition The diagnosis in this group is more apparent and the factor of ruling out carcinoma is less acute In the nonhormonal, or spontaneous group the lesion is more subtle. It is usually imllateral and a history of ono to three months duration is frequently given Nipple secretion is rare and pain is mild A disconcerting feature is a small, hard, disk or button like tumor felt directly beneath the nipple and areola which on firm palpation may be quite tender The breast is moderately or greatly enlarged and the tissue shows a diffuse, mild thickening and infiltration which Is easy to differentiate from mere fatty infiltration Axillary nodo enlargement It is this form which the surgeon is called upon to treat so that he can rule out the presence of cancer by excisional biopsy It should include the subareola, Wish liko tumor Alany patients are also concerned because of the cosmetic factor and it is safe to say that surgery is performed as much for this reason as to rulo The condition however is a reversiblo ode in some patients, and (17) is not present out ancer ·18 Gynecomastia unless the diagnosis is in doubt or the appearance a factor of major concern, these patients are best left to routine follow up examinations without surgical intervention Despite the separation of gynecomastia into two general groups qualitative differences between unilateral and bilateral gynecomastia or between hormonal and nonhormonal gynecomastia have not been observed 6 The etiology of the condition is obscure but it is fashionable to claim as a cause a hormone imbalance marked by either an excess of estrogens or androgens Even in the nonhormonal group the condition could be due to an imbalance that cannot be detected with the most sensitive criteria available today In a considerable number of patients gynecomastia arises during liver disease, malnutrition, and chronic debilitating illnesses all conditions related to the poorly understood entity called hyperestrogenism 1,2 In the latter the diseased or “sluggish” liver cannot inactivate estrogens which in turn affect breast tissue Some patients with gynecomastia do respond to crude liver extract and vitamin B comple(sce p 28) and in the selected case such a trial is considered worthwhile Best results with this form of treatment occur in boys at the age of puberty Surgical Technique of Treating Gynecomastia The patient is placed supine on the table with the arm extended at right angles (Plate 15) An incision is made which surrounds the areola on one-half of its circumference and is extended outward for 2 cm on each side (Plates 15 and 16) The nipple, areola and adjoining tissues are undermined completely forming an inferior flap (Plate 16) The same is done in the opposite direction, cyposing the entire underlying breast tissue (Plate 17) Using a large towel clip (optional) the breast tissue is grasped (Plate 17), held upward and dissected free The button-like tumor is encompassed in the grasp of the towel chip but not penetrated. The breast tissue is dissected off the underlying pectoralis major muscle which forms the floor of the dissection (Plate 18) The specimen is submitted for frozen section analysis If benign, the deep tissues are approximated (Plate 19), and the skin cdges sewn together with vertical mattress sutures of fine silk A dram is placed at one end of the wound (Plate 20) It is removed the following clay

·Gimccomastia
10
PLATE 15
PLATE 16
GEIC
1

·50
Gynecomastia
PLATE 17
í
-
PLATE 18
-
1

·Gymecomastia
51
PLATE 19
PLATE 20

·52 Gynecomastia BIBLIOGRAPHY 1 BISKIND, GR, and BISKIND, MS Nutritional Aspects Endocrine Disturbances, Am J Clin Path , 16, 737, 1946 2 BISKIND, MS, and BISKIND, GR Vitamin B Comple, and Estrogens, Endocrinology, 31, 109, 1942 3 JAASKELAINEN, V Tumors of Male Breast, Ann Med Exper et Biol Fenniae, 29, (Suppl 4), 1, 1951 4 KARSNER, H T Gynecomastia, Am J Path , 22, 235, 1946 5 MENVILLE, J G Gynecomastia, Arch Surg, 26, 1054, 1933 6 SIRTORI, CARLO, and VERONESI, UMBERTO Gynecomastia, Cancer, 10, 645, 1957 ·Chapter 5 SPONTANEOUS ABSCESSES AND DRAINING SINUSES Tus condition is frequently seen in men, especially if the source of abscess is actually tho glands of the overlymg skin rather than the breast tissue. Incision and drainage is all that is necessary as they resemble abscesses clsewhere in the body In women, abscesses will develop spontaneously on the basis of chronic cystic mastitis Intense engorgement and thichcolog of tho duct system with extravasation of intraductal secretions into the surrounding breast tissue with secondary infection will cause a major abscessed condition These occur with or without lactation Spontaneous ripture will often occir especially if the abscess is near the nipple or areola margin Persistent, drainmg sinuses dovolop and in some patients continue for years After incision and drainage, antibiotic therapy and other ancillary measures, such as compresses most abscesses disappear Hovever whero a persistent sipus remains, complete local arcision of the entire involved area seems to be the only treatment which will suffice When tho stnus tract is near the nipple excision must include the underlying tissuo in this region, sometmes extending directly upwards into the nipple itself as the Infected, granulomatous focus may lie hidden in tho base of the nipple Efforts to recover acid fast bacilli, fungus or other esoteric organistas from the tract have met with failure The involved aren is only moderately painful, usually will discharge intermittently for a few days, then disappear only to recur again in another week or two It is problematic whether the discharge increases or decreases with the ovanan cycle Surgical Technique of Treating Draining Smuses In the largo majority of patients draining sinuses treated as described under Papillomas of the Duct (page 35) heal without incident. Excision must be generous and include tissue at the base of the nipple In rare cases there is persistent drainage despite adequate local ercision This is a source of much anxiety and annoyance to both patient and physician When extreme a resection of the entire areola and nipple duct system may be necessary The technique of this procedure is outlined in the accompanying diagrams An elliptical incision is made which surrounds the entire areola and nipple (Plate 21a) and extends across the dependent portion of the brenst The shin edges are undermined and the deeper tissues mcised (Plate 21) dotyn to the (63)

·54
PLATE 21
Breast tissue
Assistant
Spontaneous Abscesses and Draining Sinuses
a.
Skin and underlying
fat reflected
operator

·PLATE 22
Pectoralis major
muscle
Block of skin, fat and
breast fissue
Meatus of sinus fract
Nipple and areola
Spontaneous Abrcses and Draining Sinusos
-
55

·56
Spontaneous Abscesses and Draining Sinuses
PLATE 23
Closure of deep
layer
PLATE 24
Small soft
drains

·Spontaneous Abweates and Draining Sinuset 57 pectoralis major muscle (Plate 22) A large block of involved tissue is removed (Plate 22) Frozen section exammation is made to determine the exact nature of the diseased tissue If benign the deep layers are closed (Plate 23) and vertical mattress sutures of fine silh are used on the slan Small soft rubber drains are placed at both ends of the wound (Plate 24) Although the possibility of cancer is rare in patients with persistent draming slouses it should be kept in mind, and a ndical mastectomy performed immedi atly when indicated. For this reason frozen section examination is made on all breast tsue excised ·Chapter 6 BREAST CANCER The voluminous studies on cancer of the breast point to its intense interest on the part of surgeons, internists, endocrinologists, pathologists and radiologists Throughout the past half-century there have been iecurring episodes of 1 encwed study of this disease At the piesent time, through the piovoking report of McWhirterºs, there is another flury of re-evaluation, review of techniques, and conscientious soul searching Recent innnovations of Urban 38 and Ariel impioving and enlarging on the classical radical mastectomy of Halsted" present a new challenge in judgment and technique to the surgeon. There also has developed a more basic interest relating to the physiology and endocrinology of breast cancer, stimulated by the work of Huggins10 17 on the adrenal glands and of Luſt and Olivecrona?on the pituitary Notwithstanding all this, paramount interest to the practicing surgeon still lies in early diagnosis and treatment. These two factors remain all important despite the valuable report of MacDonald25 on biologic predeterminism of human cancer, which points out the very variegated pattern of mammary carcinoma It would seem that for this very reason early treatment and diagnosis were of primary The fact that cancer of the breast despite much lay education, still remains the second greatest cause of death from cancer among women should call for redoubled efforts Admittedly, there are patients with breast cancers that cannot be cured by any method On the other hand, there are many who carry a poor prognosis because they have advanced disease when first treated Since the majority of breast cancers adhere to a known pattern and life history, early diagnosis and treatment still will enhance the outlook Certainly the surgeon confionted with a suspicious breast lump cannot delay biopsy Even though the fair and erudite, statistica report of Lees and Lees 20 may show that all our efforts in the treatment of breast cancer do not alter the survival rate, to the patient with a lump in the brcast, and to the many patients surviving decades after their treatment, the surgeon's efforts are of vital practical concern On the basis of personal experience and published reports 1,11 carly diagnosis and treatment are recommended as factors favoring prognosis, and until a truly workable, physiologic cure for mammary carcinoma is discovered radical mastectomy, of the type developed by Ilalsteci, remains the preferred method of treating breast cancer One muy infer from ( 58 ) concern ·Breast Cancer 9 this that mammary cancer in women has been conquered and all surgeons concerned satisfied with the results Nothing could be farther from the truth Elsewhere in this book appear other methods and techniques which strive to show how results may be fmproved and morbidity curtaled. Diagnosis There are several factors other than physical characteristics which are of help in determining the nature of n breast nodule Paramount among theso is the age of the patient Cancer is most commonly seen between the ages of forty and slty it is infrequently seen in women below thuty fivo and occurs less frequently in women who still have normal ovarian sccretion Large statistical studies show a higher mortality rate from mommary ancer in single women over thirty years of age than in married women The incidence of breast cancer in married women is higher in those wbo have never borne children in those women who bore cluldren there is a higher incidence of breast cancer in those who did not purse them Patients who havo had previous benign tumors Abroadenomas cystic disease and duct papillons show a higher Incidence of subsequent cancer on statistical studies (see p 31) The influ ence of heredity on breast cancer is debated, but the presence of breast cancer in mother and then daughter is not unusual and deserves emphasis of the many factors which are of etiologic significance in the causation of breast cancer its occurrence in the opposite breast is most important Such an incidence has becn estimated to be as high as 75 per centre in some series The patient who has had one breast involved by cancer should be viewed with especial suspicion on finding a nodule in the remaining breast llore will bo said on this subject below (sce p 83) With education of the Iny public at such a peah, the classical picture of a large hard, Arm tumor which causes overlying skin nod nipple retraction is not frequent. The diagnosis of such a tumor should be obvious to all doctors, and it presents no problem. It is the small tumor that gives for characteristic signs and which is diagnosed in the laboratory after its removnl that is worthy of empha Tuinors under 2 con in size, and without axillary node metastasis, nro problems in diagnosis and demand carly removal and microscopic examination When the diagnosis is microscopically confirmed specific therapy may be outlined Operability There are many contraindications to performning 1 radical mastectomy Somo of these are obvious, a fay more subtle When confronted with a debatablo problem which may or may not be best treated surgically one is often reminded of the stateinent of Adair 3 "Well doctor what better treatment have we to offer? There are, of course, other ways of treating concer of the breast, and ·60 Breast Cancer ) well meaning surgeons, by injudicious choice may possibly enhance the growth and spread of breast cancer To clarify the contraindications it is best to classify them into two groups. The “obvious” and the "questionably obvious The "obvious" group, as may be imagined, is simplest Patients with the following fall into this category 1. Metastases to lung, mediastinum or skeleton 2 Large, fixed, bieast and chest wall cancers. 3 Large, ulcerated cancers 4 Intracutancous nodules extending throughout the skin of the breast and associated with a deeper lying tumor. 5. Large tumors with extensive skin edema 6 Fixed axıllar y lymph nodes, with or without arm edema, or, unremitting arm edema alone. 7. Supiaclavicula, lymph node metastases There is little disagreement among sui geons on these points They are obvious because they deal with the mechanical features of breast cancer Surgical resection should not be performed when the cancer and its metastases cannot be cleanly circumvented A large cancer, though, if not fixed, and with a free margin underneath, is not necessauly inoperable, but one should not underestimate the infiltrative nature of these tumors Surgical intrusion into the field may only disseminate the disease further. The "questionably obvious” group is more physiological, and pertains to the finer relationships between cancer and patient. One cannot always afford to be dogmatic in this gioup because individual circumstances often alter one's opinion Patients showing the following fall into this gioup 1 Pregnancy and lactation 2 Inflammatory carcinoma of the breast 3 Relentless skeletal pain, chiefly back, without k-ray evidence of metastases 4. Advanced age and debılıty The basic factor in this group is a feeling on the part of the surgcon that metastases have already become widespead despite clinical evidence to the contrary Although this is most likely the case, it is wiser in these patients to consider each on an individual basis For example, opinions are divided 10,14,30 whether pregnancy contraindicates radical mastectomy, especially in the carly trimester If performed then, one may also consider thei apeutic abortion, although this too is debatable 39 During the later months of pregnancy there would appear to be more reason not to perform adıcal mastectomy as the ciciting factor has had too long to act (see section on Postoperative Pregnancy p 82). The general feeling, however, is that pregnancy alone does not contradicate radical mastectomy A statement of Adair that 24 per cent of pregnant women with breast cancer on whom he operated survived five years is of mterest The esperiences of Haagensen!" and IIcndricki do not support this Inflammatory carcinoma, lıke pregnancy and lactation, are best mdividually ·Breast Cancer 01 considered. Redness of half or less of the skin does not make the tumor Inoperable, and uoless it is associated with extenslie infiltration skin cderna and fixed axıllary metastases surgery is not necessarily contraindicated. Oophor ectomy and orchiectomy (m male breast cancer1.65) are recommended as prophy lactic procedures when surgory is performed for these lesions Relentless skeletal pain m the presence of a breast cancer is almost always due to metastases Roentgenological proof however may be lacking and in such instances the benefit of doubt understandably may be in favor of declaring the patient free of metastasis since to perform no operation would mean certain failure Concerning advanced age and debility one must cmploy careful clinical Intuition In dealing with cancer it is best to consider age a physiological not a chronological matter As so often happens when one compromises with the treatment of cancer because of nge the patient outlives all expectations, and tho surgeon is confronted with a now problem far worse than the original ono Despite the points brought out in this discussion patients in the "questionably obvious" group have a universally high mortality from their disease However special consideration should be given them because of the complex and intangiblo nature of their problem, and the uncertainty of breast cancer in the individual patient. Lymphatic Dramage of the Brcast The one, single most important prognostic sign of breast cancer is the number of lavolved lymph nodes found in the evilla There are nevertheless two chief lymphatic channels by which breast cancer disseminates the anllary and the Internal mammary These are diagrammatically represented in Figure 8 With inner quadrant cancers about 70 per cent will metastastze first to tho internal mammary chain, and between 20 to 30 por cent of outer quadrant cancers will do likewise after they have reached the axillary and apical axillary nodes Cancers m the subarcolar or central portion of the breast will also metastasize to the internal mammary nodes in a high percentage of cases The supraclavicular Dodes are usually not involved until both the apical adllary aod internal mammary groups have become involved first. 19 11 Normal axillary lymph nodes are relatively large, 0.5 to 1.5 cm the apical adllary nodes smaller internal mammary nodes are very small, 0.2 to 0.5 cm normally and at times not much larger when involved by metastruis Further discussion of the lymphatics of the breast is to be found in the chapter on Radiotherapy (p 108) and Extended Radical Mastectomy (p 91) Surgical procedures for cancer have as their basic tenet the removal of primary tumor lymphatic pathways, and lymph nodes in continuity It is this factor which makes the original Halsted11 operation so effective when the disease is limited to the breast and axillary nodes If dissection of the faternal mammary chain ·62 Breast Cancer is as effective the survival rate of breast cancer should appreciably increase This will be discussed further below Supraclavicular nodes Apical axıllary nodes 20-30 Axillary nodes 2d intercostal space Internal mammary nodes in! mening To opposite breast Epigastric nodes ay The heavy FIG 8 --Diagram of the chief pathways of lymphatic spread of breast cancer arrows show the more common routes, the broken arrows the infrequent routes. 1 Choice of Operation The Halsted'l or Willy Meyer-3 type of operation is advocated for the treatment of almost all operable breast cancers There are circumstances, however, where one may desire to change this rule By increasing the standard radical mastectomy to include the internal mammary chain of nodes it is hoped that this second major pathway of lymph borne metastases may be removed with resultant increase in survival rates To determine the nature of these nodes is of valuable prognostic importance also Routine biopsy of the internal mammary lymph nodes is practiced by R S Handleyla at the completion of the radical mastectomy, and Haagenson" has suggested that this be performed before the radical mastecbe With tumors situated in the inner quadrants of the breast thuis a valuable procedure If the removed nodes are positive on ciamination, in (OMV inay ·Breast Cancer Indicate surgery mternal mammary dissection might be indicated On the other hand if as has been suggested by Haagensen,' a supraclavicular node biopsy is also performed, and the nodes proved to be positive for metastasis, this would naturally contra In doubtful arses, therefore one may consider biopsy of edilary internal mammary and supmclavicular nodes but this is not practiced routinely and certainly these procedures in themselves are not infallible or simple Whether dissection of the internal mammary chain is worthwhile remains to be seen. It undoubtedly is a logical form of treatment. For years it has been known that carcinoma of the breast may travel toward the mediastinum while the surgeon was directing his attention to the avilla Nevertheless, one cannot yet be sure because of insufficient time interval and study that mediastinal dissection effectively removes the nodes and pathways as it does in the aulla Ono has the uneasy feeling that to remove a segment of costal margin from the suth to the first rb is a random and possibly ineffective procedure because of the multiphcity of lymphatic pathways in this area 12.13 Radical mastectomy of the conventional type usually permits the removal of most but not all of the lymphatic pathways It probably is sufficiently effective so that we shall not gain perceptibly by dissecting the internal mammary chain The question remains whether the five and ten year survival rate following Urban 510 procedure will differ appreciably from those for the standard procedure (sce section on Results of Surgery p 88) Some breast cancers nro a ravaging menace and arc "inoperable and incurablo from their inception These tumors make up the vast majority of our failures, failures which could not bo prevented by mediastinal dissection (scc chapter on Extended Radical Mastectomy p 04) At the present time, therefore, when confronted with a patient who has an operable breast cancer and on physical and roentgenological cramination shows 10 evidence of metastases which contraindicate surgery the author proceeds with a radical mastectomy of the conventional type without preopertive biopsies In another section of this book (sce chapter on Radiotherapy p 110) there is a radiological method of treating the intemal mammary nodes which represents a mtional and practical means of managing this aspect of breast cancer without surgery There are existing circumstances also which may compel one to do less than a standard radical mastectomy for operable breast cancer As a general rulo, breast cancer in the aged, scienty five and over is slow growing and slow to metastasize Simple mastectomy is worth considering in these patients when expected longevity is short and physical condition ensy whilc perform mg a stuplo mastectomy to remove many of the lymph nodes from the lower axilla. If thoy contain metastases irraduation therapy the aula could be given and may serve to dolay further dissemination for many months, oven until death from other causes takes place The method of McWhirter* simple mastectomy and axillary Irradiation is fully discussed in the chapter on Radiotherapy (p 113) This method too, represents a deviation from radical master tomy and is to be considered in selected cases poor It is ·64 Breast Cancer The procedure of simple mastectomy alone is not generally recommended In the average operable case of breast cancer it is inadequate, and for the so-called benign or “precancerous” lesions it is unnecessary Nevertheless, it is applicable in special instances, as above mentioned, and it is successfully employed as a palliative procedure to remove foul, ulcerative, fungating tumors, to remove excessively large and pendulous breasts because of non-ulcerative tumors, and possibly as a prophylactic procedure following cancer in the opposite breast More will be said on this point latei (see page 83) ·Breast Cancer 05 SURGICAL TECHNIQUES OF SIMPLE, MODIFIED AND RADICAL MASTECTOMY Incisions The recommended incisions for surgical removal of the breast arc outlined in Plates 25a and b 26 27 and 28 When a staple mastectomy is to bo These performed incisions as diagrmed in Plates 250 and b are preferred. Incisions, along with tho undermined arca totally encompass all of the breast tissue They differ from the radical operation only in the length and width of the skin ellipse Undermining and shin flap formation are considered essentini in simple brcast removal Plates 26 and 27 show the inasions recommended for a modified radical and a radical mastectomy The upper end may start at the summit of the shoulder (Plate 26) or curve beneath the arm acToss tho axilla (Plato 27) The scar is not so unsightly if this latter method is used, but rxillary exposure is slightly more difficult In patients with inner quadmnt anncers indsions such as shown in Plate 28 Rro recommended. The medial portion is cured sharply to circumvent the cancer This makes it necessary to bring the lateral portion closer to the midline of the breast Such incisions are used when internal mammory node dissection is contemplated There should be a comfortable, wide margin between tumor and incision. If there is skan dimpling ten or more centimeters on each side is not unreasonable Under no circumstances should one partou the skin ellipse because of a desire to close the wound primarily without skin grafting All surgeons must be ready to perform n skin graft to obtain adequate closure if the wound edges do not approximate without tension These focisions are only recommended Transverso incisions, upright "T typo and Inverted "Tº types are also frequently used with good healing The essential criteria of a good incision for breast amputation require that deep undermining of the skin flaps may be easily performed, and the axilla widely aposed Many incisions fulfill these criteria The surgeon will find it necesmary to chango the type of incision to fit the Individual patient Skin Flaps and Undermining Following the incisions towels are applied to the skin margins and secured with towel clips (Plato 29) The biopsy site is similarly covered (Plate 29) The lateral flap is doveloped first (Plate 29) using fine dissection technique just beneath the skin This forms a truly thin skin flap which is dissected to the edge of the latisstunus dorsi muscle In the simple mastectomy the flaps are not undermined as deeply as in tho modified radical or radical operation. The medial skin flap is made nest (Plate 30) carrying the dissection down to tho underlying pectoralis major muscle Superiorly the dissection reaches the 5

·66
Breast Cancer
PLATE 25
<
2
Incision---
Incision
Undermined
area
Undermined
area
b
PLATE 26
Skin reflected to
sternal margin
more
forenin
Incision
ga
Undermined
area

·Breast Cancer
07
PLATE 27
Incision
Undermined
area
PLATE 28
mere
Skin reflected to
midline
Incision
Undermined
area

·68
Breast Cancer
PLATE 29
Latissimus dorsi
Towel chips
a
PLATE 30
Pectoralis major
Axillary
orir vein

·Breast Cancer 69 clavicular portion of this muscle medially to the sternal margin (Plate 30) Upward traction on the towvel clips by an assistant wall facilitate elevation of the medial flap Suplo Mastectomy With lateral and media) Alaps developed the entire breast mass down to the underlying musculaturo is now freed Starting superiorly the breast mass is dissected off the underlying pectoralis major muscle (Plate 31) without disturbing the axillary contents The thin fascial layer on top of the muscle is usually removed with the breast. Soft rubber drains are placed at the lower angle of the incision and through a stab wound near the axillary portion of the lateral flap (Plate 39) The sound is closed with fine silk sutures Modified Radical Mastectomy Latcral and medial skin flaps are formed as described (Plates 29 and 30) dissecting more doeply and widely than when performing a sople mastectomy The breast is partly dissected of the underlying pectonlis major muscle, as far as the axilary edge so that the underlying axillary structures and costocoracold membrane us exposed (Plate 31) With largo retractors first the pectoralis major and then the pectoralis minor muscle, is retracted medially (Plate 32) exposing tho axilla It is thoroughly dissected (Plate 32 also 35A 38 37 and 38) sweeping the axillary contents downward to meet the partially removed breast lying on the pectoralis major muscle The breast and axillary contents are removed together from the underlying musculature. The wound is closed and druned (Plato 39) A stab wound drains the adllary space Rodical Mastectomy Wide and deep undermining with development of thin skin flaps is performed (Plates 25 through 30) The upper angle of the wound is retracted sharply exposing the insertion of the pectoralis major muscle on the humerus It is divided at its insertion (Plate 33) and separated from the clavicle and its stemnl Attachments (Plate 33) It is then partially dissected downward and laterally off the chest wall (Plate 31) The pectoralis minor muscle and adlla are exposed (Plate 31) The minor muscle is divided at its insertion on the coracoid process (Plate 35) and reflected downward The axillary apex is exposed and sharp dissection of the adlla is begun. (Plate 35A)

·70
Breast Cancer
PLATE 31
Pectoralis
major
Axillary otv
Rectus abdominis
they

·Breast Cancer
71
PLATE 32
Pectoralis major
Pectoralis minor
Coracobrachialis,
Lotissimus
dorsi
Yong thoracic
nerve
Clamp stripping
thoracodorsal

·72 Breast Cancer PLATE 33 Deltoid Coracobrachialis maumedicin Pectoralis minor Thoracoacromial στην Pectoralis major Kayutyan

·Breast Cancer
73
PLATE 34
Costocoracoid ligament
Axillary ory
1
Doctoralis
Minor
Perforating bronches
int mammory ary
Asctoralis major

·74
Breast Cancer
PLATE 35
Cephalic vein
Y
Pectoralis minor
Di
این امر
Axillary a tv
Subscapular atv
Lat thoracic vein

·Breast Cancer 75 The brachial plexus and great vessels are cleared (Plate 35A) The long The costothoracic nerve is identified, stripped and preserved (Plate 36) humeral bundle is swept downward, usually with a clamp (Plate 36) exposing and clearing the subscapularis muscle and a margin of the anterior serratus (Plate 37) The thoracodorsal nerve is identified and preserved, the thoracodorsal vessels divided, the axillary contents dissected doymard clearing further the subscapularis muscle (Plate 37) The pectoralis minor muscle is dissected off the chest wall to meet the partially reflected pectoralis major (Plate 38) The axıllary contents are dissected further downward and meet the mass of freed pectoral muscles and breast (Plate 38) The entire specimen is dissected off the underlying anterior serratus muscle and chost wall. The wound is closed (Plate 39) A soft rubber drain placed in the axillary space through a stab wound and another dram placed at the lower angle of the incision provide adequate drainage PLATE 36 X Long thoracic nerve Castanumeral bundle

·76
Breast Cancer
PLATE 37
۔۔۔
Serratus ant
lang store
Long thoracic
nerve
Thoracodorsal
nerve
Subscapularish
1
1
Axillary fali
lymph nodes

·Bread Cancer
77
PLATE 38
Serratus ant
Subscapularis
Latissimus
dors
Long thoracic
nerva
Thoracodarson
nerve
Pectoralis
minor
Roctus abdominis
External oblique
PLATE 39

·78 Breast Cancer Postoperative Care and Complications Postoperative care and complications following radıcal breast surgery are best divided into immediate and latent classifications The latter group includes lymphedema and lymphangiosarcoma of the arm, future pregnancies, management of the opposite breast, and the problem of recurrences These will be discussed individually later. In the immediate group are items such as, control of hemorrhage, avoidance of infection, proper wound drainage, lessemng of anesthesia morbidity, motion of the arm, psychic trauma and proper diessings All of these are easy to control in the smaller, biopsy procedures. However, there may be difficulty following the radical and extended adıcal operations. Blood loss at operation must be replaced by transfusions Despite meticulous hemostasis duing surgery there is a prolonged, slow oozing following the radical operation so that further blood loss occurs after the patient ieturns to her room Shock may occur and its onset will be insidious Close observation, therefore, is necessary during the immediate recovery period. For this reason it is preferable lo bind the wound (chest wall) tightly with a heavily padded, bolster type diessing, wapped around the patient with 6 inch bias stockingette (Fig. 9) Thus li Har I - Diagram show my large trip around dressing with ljstock matte lote free irm ·Breast Cancer 79 controls oozing better than applying suction catheters under the skin The bolster dressing also enhances healing of thin skin flaps It is applied over these as one does with free skin grafts, pressing the flaps against the underlying chest wall. This large dressing is not disturbed for four to five days at which time it is removed, the drains shortened, and a ney one re applied After the fourth to fifth day new dressings are applied as needed, depending on the amount of serous collection benenth the Aups This may be prolonged and considerable i obese patients, and every cffort is made to drain it off as it collects The original dums are removed in a week, aspimbon of serum through a large gnuge needle and syringe is carried out thereafter A dressing such as this is kept on until all SOTOUS collection beneath the flaps has ceased. Proper attention to sterile techniques, the use of antibiotics not routinely but as indicated, and adequate drainage will keep wound mfrctions to a minimum. Early ambulation is practiced in all causes Motion of the arm is started immediately Although the dressing is large and bulky the arm is hept frec, elevated on one or two pillows and active and passive motion instituted the day of surgery Stretching and reaching exercises are given regularly throughout the entire hospital stay Following the radical procedure there is, of course, much psychic trauma which in some cases can be marked. However in no instance has this resulted in any thing more than a transient depression By the tme the patients leave the hospital, usually within a week, most will have adjusted well. With cncourage meat, and after meetmg other patients with similar difficulties, tho problem seems to resolve itself A prosthetic applianco is wed as soon as healing is complete. Postoperativo Ray Therapy Until the reports of McWhirtero there had been wading enthusiasm for the uso of postoperative i nay therapy Following the radical operation it had been customary in some clinics to treat the builla, the supraclavicular area, and the chest well with varying anounts of radiation on the supposition that any loose or remaining cancer cells would be destroyed and the results enhanced. This how over was not the case Increased arto edema, and painfully sore areas of radiation dermatitis vero all too frequently encountered as well as an under lying pulmonary fibrosis which used intractable coughing Other surgeons used postoperative iradiation in selected cases, mther than as a routino procedure." tho decision to use frradiation depending on the dogree of involvement of the arlllary lymph nodes With the adient of VicWhirter som method, namely simple mastectomy and axillary Irradiation, and also due to the increased attention being given tho Internal mammary nodes, surgeons and radiologists have been forced to recvaluate irradiation therpy Today hen I ray treatment is given postoper atively it is concentrated primarily over the apical axillary internal mammary 7.30 ·80 Breast Cancer 1 and supraclavicular areas Areas which the surgeon cannot ordinarily reach with the standard operation There seems no purpose in directly irradiating an aulla which has been thoroughly dissected Öne relies on competent surgical technique to remove operable aullary metastases The chest wall is not irradiated either X-ray therapy to these areas is reserved solely for local, nodular recurrences The following considerations are, therefore, made regardmg postoperative 2-ray therapy 1 Patients with cancers in the outer quadrants and who have no aullary lymph node metastases receive no postoperative irradiation 2 Patients with cancers in the inner quadrants, however, who have no aullary metastases do receive irradiation to the internal mammary and supraclavicular areas 3 Patients with cancers in the outer quadrants who have axillary metastases receive irradiation to the apical axıllary, internal mammary and supraclavicular areas 4 Patients with cancers in the inner quadrants who have aullary metastases receive irradiation to the apical ayllary, internal mammary and supraclavicular areas This policy, which reflects numerous combined surgical opinions, as well as those of the Stanford University Hospital Department of Radiology (sce chapter on Radiotherapy, p 109) has been practiced for the past five years. Whether the results with inner quadrant lesions will equal those treated by mediastmal dissection remains to be seen, but until more concrete evidence for dissecting the mediastinum is revealed this policy will continue (sce chapters on Results of Surgery, p. 88 and Extended Radical Mastectomy, p. 94) Adjunctive Procedures It is quite apparent that surgery is not the sole answer to the present treatment of breast cancer Ancillary procedures which may increase survival times must be considered and used In 1896, Beatson' suggested the possible beneficial effect on breast cancer by removing the ovaries The subject is controversul not because of the validity of lus report, there is benefit derived from removing the ovaries, but because of the timing of the castration A definition of terms is important Prophylactic removal of ovarian fimctius is described as that which is donc just before or immediately after mastectonis and before recurrences or metastases, other than wllary or internal mammary nodes, take place Therapeutic removal of ovarian function would be that pur. formed „fter distant met.stases and recurrences occur The only phase of this subject which is not heavily debated in the methori of removing ourian function Surgical castration today is to be furore never 1-Jily, although the latter method has its advocates toon (sep 118) Contramento, ·Breast Cancer 81 or the presence of skeletal metastases in the pelvic bones, may weigh in favor of immdiation This way one would include the ovaries in the I ray port covering the bony metastasis Nevertheless surgical castration is quicher more complete, and in the long run probably less painful. To remove the ovaries in the premenopausal group is a matter for ndividual study The recent report of Troves 17 which is most completo, concludes with the statement that "in our mind it is still an undecided problem whether it would bo advisablo to reservo austration for therapeutic uso when need anses, or whether to view of the prolongation of life as indicated by this study surgical castration should be wed as a prophylactic procedure in all causes with very guarded prognosis. In his series tho survival rates of patients surgically castrated appear to be improved at the five-year level This improvement was espedally notable among those patients with node involvement. Horsleyls made an extensive study of the subject and also found that prophylactic castra tion did result in a higher five year survival figure especially in those patients with node ini olvement, than in the noncastrated group Contrariwise, there are others who could find no essential difference in the two groups Because of the lack of concrete evidence the independent surgeon is forced to individualize, and reserves prophylactic castration for the more serious or prognostically bad patients It is difficult to prove any noticeable difference between the two methods It might be best to withhold castration until it is therapeutically necessary especially since this is not a curativo procedure and In itself is not a minor matter The response of bono metastases to castration alone is sometimes very gratifying Since thero are only a limited number of bullets" with which to treat disseminated breast cancer one is reluctant to "fire them off" quickly but rather conserve them, and use them slowly assessing the value of each and not using the next until the previous one has been tried. One s strategic retreat" seems better covered in this manner in the postmenopausal group vaginal smears are examined for evidence of estrogen activity If positivo therapeutic oophorectomy would be performed when indicated by the presence of distant metastases (see chapter on Hormone Treatment, p 122) With patients Am Lymphedema Practically all patients who have undergone a radical mastectomy will der elop some degree of stelling of the arm It appears to a lesser degree in patients under thirty five years of age. Xleticulous dissection about vessels, many of which are clamped and ligated, removal of lymphatic channels scarring and Abrosis with diminished venous return, normally causes arm edema Such factors as postoperative infection, irradiation, or occult mediastinal metastases also tend to enhance tho condition Obese patients seem to suffer more than thin ones In addition there is an idiopathic or unknown factor as well *Limphedema is much less frequent following radical mastectomy in men 0 ·82 Breast Cancer The swollen arm is easily affected by a peculiar, red wave of cellulitis and mfcction, termed “erysipeloid,” which responds readily to antibiotic therapy, as well as elevation and warm compresses The lymphedema, once pronounced, is progressive up to a point from which there are occasional partial remissions but never to normal Treatment of the acutely inflamed phase is similai to that of any inflammation but there is no magic formula which will reduce the lymphedema once it is established Adequate, firm postoperative dressings, proper diamage, an mſection free wound and early arm motion and exercise may tend to curtail or diminish this complication Suction catheters under the skin flaps postoperatively have made no difference Muscle transplantation of the latissimus dorsi across the dissected aulla is recommended by somel4 18,4" but has not proved popular, and is of doubtful help It serves to obliterate the dead space across the dissected aulla, and possibly provide a tissue bridge for regenerating lymphatic channels It may be of use in cases of obesity where lymphedema seems to be almost the rule In 1948 Stewart and Treves 32 reported on 6 patients with lymphangiosarcoma developing in the lymphedematous arm There have been other reports of this condition since then It is a very aggressive, vnulent, malignant lesion which develops long after the mastectomy (average twelve years) It starts in the chronically obstructed lymphatics and presents as a “purplish-red, suhtlermal, slightly raised, macular or polypoid lesion on the skin of the armi neair the anticubital fossa ?? It is solitary mtially, but gets confluent with other areas, The lesions becomc nodular, may ulcerate, heal and break down again, and) cventually cover the entire extremity with spread onto the adjacent chest wall Radical amputation of the arm and shouldei girdle is the preferred method of therapy, if feasible Metastases are pulmonary Postoperative Pregnancy It has already been noted that cancer occurring during pregnancy or lactation does not in itself contraindicate a radical mastectomy. What llien should lic the advice of the physician to the young woman who contemplates marriage and family after her operation? Little doubt custs that there is a stimulating effect of pregnancı on brooist The fact also cysts that cancer cells may lie dormant or "ocherla in okolf tissue for years and that a scemingly “cured" patient may actually harbor m.1110 foci of recurrent cucer The occasionally long dormant interval betu con opera. ton and distant metastases, sometimes ten or more vours afterward, tends to emphasize this point And since there is a 110 S per cent chance of the opposite breast becommg culcerous un occult lesion here occurring during pregnallll! would further love's the prognosis Iso recommendations with reference to prophylactic Custration would have to be discounted were prone to bringered Cancer ·Breast Cancer 83 as a complicating factor Moro specifically the outlook of patients whose tumors Were noticed during pregnancy but were allowed to deliver first, and then had their operation, is worse than thoso patients who had immediate surgery per formed during their pregnancy The same may be said of those patients developing cancer during the nursing period, that is, those who have immediate surgery without delay do better The key pomt in this group of patients is the extent of the breast cancer at tho time surgery is performed This, in general, is largely determined by the number of adllary lymph nodes (or internal mammary) involved. It has been shownto that patients with cancers limited to the breast will do well despito pregnancy or nursing However those with axillary nodo involvement do very poorly ** If therefore, a patient has no axillary metastases (and one may say Internal mammary node metastases on the basis of location of the lesion) at the time of her operation future pregnancies would not be contraodicated. On the other hand, patients who did have adllary node involvenent would be wisest to avoid pregnancy in the future at least until an arbitrary interval of three to five years The Opposite Breast Each breast is subject to the same physiologic environment, and each breast is basically and inherently similar to the other Yet the realization that these tivo organs may in fact be considered as one is slow in gaining acceptanco There is now however an increasing awareness that the results of tho surglal treat ment of breast cancer may be enhanced by simple mastectomy of the remating brcast The incidence of unsimultaneous primary cancer of the opposito breust is between 4 and 8 per cent.At times, it is not easy to bo certain whether one is dealing with a primary tumor or a metastasis Histologic study will not differ entlato these lesions Naturally if each tumor is situated in the inner quadrants more doubt would exist as to the independent nature of each. On the other hand, In a patient with two outer quadrant cancers and no evidence of local or distant metastasis or recurence ono may fairly assume them to be unrelated. Involvement of the second breast by metastasis is uncommon without other evidence of metastasis or recurrence as well Given a patient, therefore with tumors occur ring sit or moro months opart, and no other evidence of recurrent or metastatic cincor the probabilities are likely that one is dealing with an insimultaneous second primary lesion Simultancous cancer in each breast is less frequent but should be considered The ideal management of a patient with simultaneous operable cancer in cach breast is bilatemni ndical mastectomy stnged five to ten days apart This may not be feasible in every Instance and combinations such as radical and simplo mastectomy with or without postoperative I ray therapy can be used The same is to bo eid for the patient who develops another primar at a later ·81 Breast Cancer date, that is, a second radical mastectomy is ideal But, with a patient who has a diminished prognosis because of cancer in one breast, an impaired physiology, an increased morbidity, and the possibility that this second tumor could be a metastasis, the surgeon is justified in modifying the second procedure to a less radical operation in order to curtail postoperative discomfort and complications When, therefore, some doubt eusts as to the curability of the patient, or the exact etiology of the second cancer, a simple mastectomy with aullary dissection would be preferable to radical mastectomy If the nodes are positive postoperative a-ray therapy is usually given One cannot help but feel that a patient who, for example, has had one breast removed because of cancer with audlary node metastases, and then develops another cancer in the opposite breast, probably cannot be cured unless the second cancer is limited to the breast itself Dissecting out the aullary nodes serves a therapeutic purpose, of course, but an additional advantage is in determining the extent of the cancer Morbidity is greatly reduced by following this more conservative approach and with little change in survival rates 22 Because of the significant incidence of another cancer in the opposite breast prophylactic simple mastectomy has been advised either at the time of performing the radical or after a waiting period of two ycars The latter period is an arbitrary time limit to determine whether the patient has a reasonable chance of being cured of her cancer before undergoing further sugery No matter how logical this sounds it would seem that if prophylactic measures are to be undertaken the sooner they are performed the sooner they ciert then effect, and that they might lose their effectiveness were one to delay the procedure beyond a few months after the radical operation In other instances prophylactic simple mastectomy of the opposite breast has been used selectively in those patients with strong family histories of cancer, in child bearing age groups where further children are desired, or in medially placed cancers Unfortunately, despite its advantage to the average patient with breast cancer, prophvlactic simple removal of the second breast is viewed with abhiorrence liv most patients and, thus far, has been seldom performed Nevertheless, with the patient who after frank discussion has no objections, the procedure should be performed and would prove worthwhile It should be discussed with all patients 8 operation” Treatment of Recurrences There are other chapters in this book which deal fully with the mungeni nt and treatment of breast cancer recurrences (ser chapters on Ruliothie rap, p 16 Florinone's p 122 Adrenalectomy, p 124 nu llypophyseetom, p 139), but there are seas crial fundamental concepts which mit descrission at this name Todas patients with breast cancer ariscon 21 .1) crlier stage of their else 144 and lip loc il recurrence rite is for less than yours.go, thus cespite the mteupane SKY of nating for wound closure Concurrently, improved techniques fuse lo ·Breast Cancer 80 reduced this complication Chest wall recurrences present as 9 to 5 mm., subcutaneous nodules along the scar If they are so situated that they can be acised thus is ideal As a rule they do not lend themselves to clean excision and tradi ation of the zone or area is usually better The same is to be said of Axllary recurrences Surgical acision of these nodules may run the risk of further disseminating the disease and break down the scar barriers which tend to curtall its spread. At this timo therefore, chest wall and direct axillary radiation play a major therapeutic role. The supraclavicular area would have to be included if nodo enlargement is found (sce p 116) It is to be emphasized that the best method of treating distant breast cancer metastases or local recurrences is with Irradiation. This is especially the case when one is confronted with a localized sheletal or lymph node metastasis Relſef of pain and regression in sizo of the tumor is usually rapid As the disease progresses one then employs more systemic measures. Theso in turn are oophorectomy oral or parenteral bormones, adrenalectomy and finally hypophysectomy Not until metastases or recurrences become generalized is oopha rectomy perfonned in the premenopausal women and in those postmenopausal tomen who on vaginal smears show signs of estrogen activity Following this procedure it is worth waiting for several weeks to months to evaluate the effect rather than combine it with oral or parenteral use of hormones. Removal of the adrenals and the hypophysis is reserved for those patients with moro advanced disease, and after oophorectomy and parenteral hormoncs have been given ample trial, Carcer of the Malo Breast Tho considerations which have been discussed with referenco to cancer of the female breast apply equally as well to the male The incidence of male breast cancer is under 1 per cent It is seen in a later age group than in women, yet the prognosis is felt to be more guarded. Similar histologic types of tumors occur in the malo breast, including inflammatory carcinoma and Pagets disease of the nipple The breasts of male patients who are undergoing estrogen therapy for prostatic cancer should be closely watched for the developmont of cancer as a complication Orchlectomy is recommended as a therapeutic measure for treating skeletal and soft tissue metastases and recurrcnCCS The responso to this procedures with male breast cancer seems to be more favorable than oophorectomy in female breast cances There is no response to estrogens after the effect of orchiectomy has subsided Adrenalectomy and hypophysectomy may be worth consideration should the tumor give evidence of hormone dependency BIBLIOGRAPHY 1 ATAT LV Evaluation of Breast Cancer Treatment by Dr R Vell'hinter Cancer 8 883 1955 ·Breast Cancer LDAIR, F E American College Surgeons Symposium, San Francisco, 1951. Personal communication RIEL, IM Conservative Method of Resecting Internal Mammary Nodes, Surg, Gynec & Obst, 100, 623, 1955 SEATSON, GT Treatment of Inoperable Carcinoma of Mamma, Lancet, 2, 104, 162, 1896 YRD, B F, and STEPHENSON, S F Simple Mastectomy, Ann Surg, 145, 807, 1957 ancer of Breast at Mayo Clinic, Proc Staff Meet, Mayo Clin , 32, 645, 1957 OBSON, L Bilateral Breast Cancer, Stanford Med Bull, 13, 456, 1955 (AAGENSEN, C D Diseases of the Breast, Philadelphia, WB Saunders Co, p 377, 1956 (AAGENSEN, CD, and STOUT, A P Carcinoma of the Breast, Ann Surg , 134, 151, 1951 (ALSTED, WS Results of Radical Operation for Breast Cancer, Tr Am S A, 25, 61, 1907, (reprinted) Ann Surg, 46, 1, 1907 (ANDLEY, RS Internal Mammary Lymph Chain, Proc Roy Soc Med, 45, 565, 1952 Internal Mammary Lymph Chain, in SANER, F D The Breast Structure, Function and Disease, Baltimore, The Williams & Wilkins Co, p 201, 1950 ENDRICK, ) Carcinoma of the Breast, Ann Surg , 146, 728, 1957 ORSLEY, GW Cancer of Breast and Oophorectomy, Ann Surg , 125, 703, 1947, and Virginia M Month , 78, 226, 1951 UGGINS, C, and BERGENSTAL, DM Inhibition Human Mammary Cancer by Adrenalectomy, Cancer Res, 12, 134, 1952 UGGINS, C, and Dao, T L Y Adrenalectomy and Oophorectomy in Breast Cancer, J AMA, 151, 1388, 1953 UTCHINS, EH Prevention of Elephantiasis Chirurgica, Surg, Gynec & Obst, 69, 795, 1939 ILGORE, A R Precancerous Lesions of the Breast, West J Surg , 40, 581, 1932 EES, J C, and LEES, T W Numerical Estination in Cancer and Cancer Treatment, Cancer, 3, 377, 1950 UFT, R, and OLIVECRONA, H Hypophysectomy in the Management of Neoplastic Disease, Bull New York Acad Med , 33, 5, 1957 edical Forum Bilateral Breast Cancer, Modern Medicine, 32, 1957 Cancer of the Breast, Surg, Gynec & Obst, 24, 553, 1917 OERTEL, CG, and SOULE, E H Problem of the Second Breast, Ann Surg, 146, 764, 1957 ACDONALD, I Predeterminism in Human Cancer, Surg, Gynec & Obst, 42, 443, 1951 cWHIRTER, R Simple Mastectomy and Radiotherapy, Brit J Radiol, 21, 599, 1948, Ibid , 28, 128, 1955 ATHANSON, I T, RICE, C, and Mrics, J V Artificial Menopause Produced by X-Rays, Am J Obst & Gynec, 40, 936, 1940 Bilateral Mastectomy, (Editorial), Surgery, 29, 929, 1951 CINHOFF, WF Muscle Flap for Prevention of Swelling of the Arm, Bull Jolins Hopkins Hosp, 60, 369, 1937 SAHN, PD Carcinoma of the Breast, A 16, 912, 195 RONG, RH, JR, and POLLOCK, WF le of Radic Ann Surg , 133, 330, 1951 'EWART, F W, and TREVES, N Lympha Cancer, 1 EYER, W ACK, GT V ini, 5

·Breast Cancer
87
33 TAYLON, GW Artificial Mercopause in Breast Cancer New England J Med.
211 1138 1934 Ibid., 213 120, 1935
34 TRIVES, N Castration in Male Braut Cancer Cancer ? 191 1949
35
Inflammatory Carcinoma of Breast in Male Patient Surgery 34 610
1953.
38.
Lymphedema After Radial Mastectomy Cancer 10 444 1857
37
Prophylactie Castration in Breast Cancer Cancer 10 393 1957
38 URBAN JA Radical Mastectomy and En bloc Retection of Internal Memory
Chain Cancer 5 992, 1952.
39 WHITE, T T., and WOTE, WC Breast Cancer and Pregnancy Ann Surg
144 394 1958

·Chapter 7 RESULTS OF SURGERY AND EFFECT OF SPECIAL FACTORS ON RESULTS NUMEROUS clinics throughout the world cite similar results in the treatinent of breast cancer despite wide differences in case selection and methods of therapy Some controversy has arisen as to whether the long accepted radical mastectomy is truly the most effective treatment20,38 or whether all methods are equally effective.36 The basic difficulty arises in comparing series which are not truly comparable Variations in selection of patients for therapy and the known inaccuracy of a classification based on clinical staging are factors which greatly influence final results Other significant factors include the age of the patient and the individual characteristics of the neoplasm, such as its histology, growth iate, size, duration, and location in the breast No two reported series contain similar proportions of tumors of different histological degree and extent of malignancy More uniformity in reporting is essential before any method of therapy can be accurately assessed The degree of malignancy based on histological grading often runs a close parallel with the extent of disease and period of survival Grade 1 lesions are not as likely to metastasize as do Grade II or Grade III lesions 12 Less than 10 per cent of Grade I carcinomas had axillary metastases while 88 per cent of Grade IV lesions were noted to have positive nodes 10 Five-year sus vival dropped from 65 per cent in Grade I cancers to 16 per cent in Grade III cancers when axillary nodes were involved In Bloom'sú series the histological grading did not vary significantly, either in separate aieas of the tumor or in the nodal metastases Certain histologic types, as medullary carcinoma with lymphoid infiltrate, have a relatively favorable prognosis when properly treated in spite of the large size primary frequently seen There is a sharp increase in nodal metastases with larger size breast carcinomas 30 Only 10 per cent of 28 patients whose tumor was less than 15 mm had positive aullaiy nodes 11 The incidence of axillary metastases with tumors over 4 cm was almost doubled that of tumors less than 2 cm 35 Survival rates in cases with axillary node involvement showed a major decline from 54 to 22 per cent five-year salvage as the size of the primary lesion increased from under 2 to over 5 cm The level of the aulla involved by tumor has considerable influence on progno- Invasion of the axillary lymphatic filter often begins in a progressive manner (88) 28,34 40 SIS ·80 Rosults of Surgery and Efect of Special Factors on Rosults at the base of the axilla and proceeds to the aper Hangensen's believes the patient is categorically inoperable when the apex is involved, since it implies the supraclavicular nodos already contain deposits By dividing the adllary con tents at the time of surgery and labelling it with metal tags, the prognosis can be estimated by the lovel of Dodlal mvolvement. Adafr' has cited 62 per cent five year salvage with the involvement of the base of the sulla, 45 per cent with the mid axla, and 28 per cunt with the apex. Opinions diffor us to whether the age of the patient at the onset of the lesion plays any part n prognosis Some observers feol that results are poorer in tho younger age groups ** ** Others believe that cancer occurring in women belovy the age of thirty especially if the axillary nodes are not involved, has a more favorable outcome 10,43 With tumors of equal watent, age probably escrts no significant influence. It is generally believed that the longer the delay in treatment after onset of symptoms, the poorer is the prognosis 20,25 Adllary node involvement was present in 74 per cent of patients who delayed twelve months before seeking treatment while only 55 per cent of patients who delayed one month bad axillary metastases Park and Leegits postulate that the time factor has not truly affected the cure rate, prmarily because there are marked variations in growth rate be tween cancers of different degrees of maliguancy Lesions that increase rapidly in size in a limited amount of time often represent the more aggressive high grade tumors and the prognosis is always poorer Evaluation of the biological behavior in terms of approximate mte of growth from the time of onset of symp toms may give some information as to ultimato prognosis Tho location of the primary lesion in the breast is thought to have a definite effect on cure rate. With a carcinoma occultmg beneath tho areola or lo the medial quadrants of the breast in proximity to the internal mammary lymph Dodes tho prognosis was significantly lower 18,44 Even whero axillary nodes were negative, the medial quadrant lesions had a five-year survival of only 53 per cent in contrast to lateral quadrant lesions with a five year survival of 75 per cent * Haagensen" found that cancers originating near the sternal border in the lower medial quadrant have the poorest prognosis and the highest recurrence rato. Others have not found significant difference in end results in relation to location of the primary tumor 1,37 A higher ſnudence of metastases to mterpal mamman nodes was present when the cancer began in the central or medial half of the breast 612,18 44 By biopsy of internal mammary nodes at the time of radical mastectomy 29 of all cases were found to have metastases to these nodes When axillary nodes Veto positive, about two-thirds of all tumors located in the medial half of the breast had internal mammary node invasion 1 The adequacy of the standard radial mastectomy in such instances is questionable and may explain the lower salvago rate. Prognosis cannot be accumtely estimated with present methods of clinical staging based on axillary involvement alone In a group of 75 patients per cent ·90 Results of Surgery and Effect of Special Factors on Results 14 in whom biopsies were taken of internal mammary nodes at surgery, three-fourths of patients with only axıllary node metastases were alive at the end of three years Only one-third of those with both axillary and internal mammary node metastases were living at three years Up to the present time radical mastectomy has yielded the highest cure rate for primary operable carcinoma of the breast With this procedure approximately 50 to 55 per cent of patients live five years When the axilla is involved, most clinics report five-year survival figures of only 35 to 40 per cent, but when the disease is confined to the breast, 70 to 80 per cent of patients are still living, free of recurrence, at five years (Table 1) At the end of ten years about 35 per Table 1.--Five-year Survival Rate in Primary Operable Breast Cancer Treated by Radical Mastectomy Number of Orerall Cases % Breast Only Inrolled % Breast Place Azilla Inrored % Memorial Center for Cancer and Alled Diseases Lahey Clinic24 Mayo Clinic17 University of Virginia Johns Hopkins Hospital20 Haagensen (Personal Series) 3494 238 8224 824 220 350 54 4 52 1 52 1 54 44 1 567 77 5 750 78 1 74 041 788 30 4 37 0 33 1 37 31 7 388 cent of patients are still alive, and in fifteen years 25 per cent are still free of recurrence If axıllary nodes were negative at surgery, 49 per cent of these patients are still living at the end of fifteen years 17 These results are often compared to Daland's10 series of 100 untreated cases in which the average duration of life was forty months and the five-year survival rate was 22 per cent The measurement of effectiveness of any form of therapy for breast lesions must improve these figures to be worth-while Some patients with apparently operable breast cancers are already beyond the scope of radical mastectomy by virtue of internal mammary and supraclavicular metastases Attempts have been made to extend the procedure and thus better the salvage rate 5,9 16 23,29,33,41,44 45 As yet, sufficient series of long-term survivors have not been reported Wangensteen's+7 experience combining a radical mastectomy with an anterior mediastinal and supraclavicular dissection in one or two stages has been disappointing and yielded a five-year survival of only 17 per cent Many of his cases were advanced at the time of surgery Dahil-Iversen has reported three-year survivals of 63 per cent without evidence of recurrence and five-year survival of 43 per cent by doing supraclavicular dissection and extrapleural removal of internal mammary nodes Margotlını" has shown in 147 per cent overall increase in five-year survival statistics utilizing an extra- ·Results of Surgery and Effect of Special Facton on Resulta 91 pleural internal mammary clissection and staged supraclavicular dissection The intemal mammary vessels and nodes were removed en bloc along with the breast and arl]lary contents by Urban“ in over 300 cases With 70 cases followed for over five years he has obtained a survival rate of 65 4 per coat, while 61 4 per cent of patients alive at fivo years have no evidence of recurrence Among these 43 clinically cured patients, 19 per cent of this group had positive internal mam mary podes at the time of surgery and 46.5 per cent had positive axillary nodes These figures are encouraging and seem to indicate there will be a definito in crease in salvage especially where the lesson originates in the central or medias half of the breast. Many other methods have becn employed to improve results of radical mastectomy Preoperative radiation therapy (see p 108) only delays and complicates futuro surgery of the breast and has produced less satisfactory end results to In the postoperntive penod radiation is usually employed when the removed nodes are found to be involved Results were slightly improved after radiation was given for axillary nodes which wero positive, but were inferior if no involvement was present"? In a group of 226 patients with positive nxillary nodes 41 per cent of patients receiving postoperative radiation survived five years while only 32 per cont of those without radiation lived a similar period. 18 Marshallas employs this program for all patients after surgery although his rosults are similar to those where radical mastectomy only was done Others ate rates which show no im provement7,10 with postopemtive mduation therapy and are, in fact, mfurior This may be due partly to the fact that patients with more advanced lesions, or with lesions with unfavorable clinical features, often comprise the group referred for radiation therapy Although present methods of treatment for breast cancer are not adequate, radical mastectomy still reinains the standard treatment. Extension of radical surgery to include those areas not encompassed by the routino radical mastectomy probably will find its greatest indication with early subareolar or medial quadrant tumors Standardization of operativo technique in performing a radical mastec tomy is to be stressed, since even today an incomplete axillary dissection or inadequnte removal of the primary tumor is seen Early detection of cancer before it is clinically obvious, carcful selection of patients for surgery and prompt treatment are other factors which will better the results, BIBLIOGRAPHY 1 ACIERIAN LV Evaluation of Treatment of Cancer of Breast by Dr R McWhirter Cancer 8 883 1955 2 Adan, F E Surgical Problems Involved in Breast Cancer Ann Roy Col Sur geons England + 360 1919 3 Cancer of the Breast, Sarg Clin N America, 313 1833 4 ALRAL E X, LIODLE, H V., and Vortor CB Carcinoma of Breast Results of Surgical Treatment, Ann Surg, 145 799 1857 ·92 Results of Surgery and Effect of Special Factors on Results 5 ARIEL, I M A Conservative Method of Resecting The Internal Mammary Lymph Nodes en Bloc With Radical Mastectomy, Surg, Gynec & Obst, 100, 623, 1955 6 BLOOM, H J G Prognosis in Carcinoma of Breast, Brit J Cancer, 4, 259, 1950 7 BRYANT, MF, LAMPE, I, and COLLER, F Cancer of the Breast, Surgery, 36, 863, 1954 8 DAHL-İVERSEN, E Recherches sur les metastases microscopiques des ganglions lymphatiques parasternaux dans le cancer du sein, J internat chir, 11, 492, 1951 9 Extended Radical Operations for Mammary Cancer, Third National Cancer Conference Proceedings, Philadelphia, J. B Lippincott Co, p 148, 1957 10 DALAND, E M Untreated Cancer of the Breast, Surg, Gynec & Obst , 44, 264, 1927 11 HAAGENSEN, C D, and STOUT, A P Carcinoma of the Breast, Ann Surg , 134, 151, 1951 12 HAAGENSEN, CD Diseases of the Breast, Philadelphia, WB Saunders Co, 1956 13 HANDLEY, RS Further Observations on the Internal Mammary Lymph Chain in Cancer of Breast, Proc Roy Soc Med , 45, 565, 1952 14 HANDLEY, RS, and THACKRAY, AC Invasion of Internal Mammary Lymph Nodes in Carcinoma of the Breast, Brit M ), 1, 61, 1954 15 HANDLEY, RS, PATEY, D H, and HAND, B H Excision of the Internal Mammary Chain in Radical Mastectomy, Lancet, 1, 457, 1956 16 HARRINGTON, S W Carcinoma of Breast with Results of Radical Mastectomy, Surg Clin N America, 21, 1063, 1941 17 Three- to Forty-Year Survival Rates Following Radical Mastectomy for Carcinoma of the Breast, Western J Surg , Obst & Gyn, 63, 272, 1955 18 HENDRICKS, J W Results of Treatment of Carcinoma of the Breast, Ann Surg, 146, 728, 1957 19 KENNEDY, B J, KELLEY, RM, WHITE, G, and NATHANSON, I T Hormone Therapy in Breast Cancer, Cancer, 10, 1055, 1957 20 LEWISON, E F, TRIMBLE, F H, and GRIFFITH, PC Results of Surgical Treatment of Breast Cancer at Johns Hopkins Hospital, 1935–1940, JAMA, 153, 905, 1953 21 MacDONALD, I, and Wilcox, N E Prognosis of Mammary Carcinoma in Young Women, Cancer, 9, 281, 1956 22 MARGOTTINI, M Discussion, Symposium on Cancer of the Breast, Third National Cancer Conference Proceedings, Philadelphia, J 'B Lippincott Co, p 177, 1957 23 The Surgical Treatment of Carcinoma of the Breast, Coll International de Chirurgiens, Volumes des rapports publie a l'occasion du XX Anniversaire, 744, Geneve, 1955 24 MARSHALL, S F, and Harr, Hugh, F Carcinoma of tlic Brcast Results of Combined Treatment with Surgery and Roentgen Rays, Ann Surg, 135, 688, 1947 25 licDONALD, J J, Haage srx, CD, and STOUT, A P Metastases from Mammary Carcinoma to the Internal Mammary Lymph Nodes, Surgery, 34, 521, 1953 20 MCWINTER, R The Value of Simple Vastectomy and Radiotherapy in the Treatment of Cancer of Breast, Brit J Radiol, 21, 599, 1918 27 MOCNTCL, C G The Problein of the Second Breast, Ann Surg, 116, 701, 1977 Surgery and ·Results of Surgery and Effect of Special Factors on Results 03 28 MOORE, O S, and FOOTI F W JA The Relative Favorable Prognosis of Viedul lary Carcinoma of the Breast Canco 2 635 1949 29 NOEL, OF Extended Operation for Carcinoma of the Breast, Surgery 38 423 1955 30 NOMIAN B A. Cancer of the Broast A Clinical Study of 1042 cases treated at the Radium hemmet 1938-41 Acte, radiol (Supp77) p I 1919 31 Pack, GT Argument for Bilateral Alastectomy Surgery 29 929 1951 32 PARE, V W. and LEES JC The Absolato Curability of Cancer of tho Breast, Surg Gynec, & Obst., 83 129 1951 33 PAUDENTE, A Lamputation Inter-fcapulo-mamtoo-thoracique ) de chur. 65 729 1949 34 RICHARDSOV IV IV Medulary Carcinoma of the Breast, Bolt J Cancer 10 415 1950 35 ROBRIN, G F and Bross, I The Significance of Dolay in Relation to Prognosis of Patients with Pomary Operable Breast Cancer Cancer 10 338 1957 38 ROSAIN PD Results of Treatment of Carcinoma of the Breast, Ann Sury, 146 912, 1957 37 SMIAN M D., LUCIA, E L., STOVE, RS And BELL, H. G Cancer of the Breast, Sung, Gynec & Obst 94 645 1952 38 SHALI, R. G., and DUTTON A Survival of Patients with Carcinoma of the Brenst, J.AMA. 157 216 1955 39 STEWART FW Factors Influencing the Curability of Cancer Third National Cancer Conference Proceedings Philadelphia, į B Lippincott Co. p 62, 1957 40 STEWART F1 Tumors of tho Breast Subcommittee of Oncology of tho Com mittee of Pathology of the National Research Council, Section E, Fascido 34 Washmgton DC 1850 Armed Forces Instituto of Pathology 41 SUGARBAKER, E D Radical Mastectomy Combined with Incontinuity Resection of the Homolateral Internal Memmary Nodo Chain, Cancer 6 989 1953 42. TAKVTS, N An Evaluation of Prophylactic Castration in the Treatment of Mam mary Carcinoma Cancet 10 393 1057 43 URBAN J A. Perronal communication 14 URBAN ) A and BAXER, H A Radical Mastectomy in Continuity with En Bloc Resection of the Internal llammary Lymph Modo Chain, Cancer 5 992 1952 45 WANCINSTEEN O H LEWIS F J., and' ARILLGER, S W The Extended or Super Radical Alastectomy for Carcinoma of the Breast Surg Clin N America 1051 1858 ·Chapter 8 EXTENDED RADICAL MASTECTOMY END-RESULTS with present methods of therapy for breast cancer indicate that approximately one-half of all cases die within five years Considerable attention today is focused on the standard radıcal mastectomy, long accepted as the treatment of choice, but which fails to remove the internal mammary lymph nodes Since these nodes are involved in about one-third of all cases, radical mastectomy is destined to fail as a curative procedure in these instances Patients with positive supraclavicular or internal mammary nodes are usually regarded as unsuitable for surgery surgery because of poor results 8 The failure of radiation to eliminate cancer in such locations has stimulated some surgeons to extend the classical radical mastectomy and encompass these areas Whether the most effective method will be surgery, radiation, or a combination of the two has not yet been conclusively demonstrated The main lymphatic drainage of the breast is primarily to the aullary and internal mammary lymph nodes From these depots secondary drainage passes into supraclavicular nodes at the base of the neck, and into the blood stream through the lymphatic ducts on the right and the thoracic duct on the left There is a rich anastomatic lymphatic plexus occurring in the subareolar area which drains into both internal mammary and axillary nodes An English anatomist, Stibbe,13 made the first complete study of the internal mammary lymphatics An average of 85 nodes were found per subject Thesc were most commonly noted in the first, second, and third interspaces but were infrequent in the fourth or fifth interspaces),13,15 When involved with cancer, nodes on the sternal side, medial to the internal mammary vessels, were positive in 82 per cent, while nodes lateral to the vessels were positive in 54 per cent " The parasternal nodes are the last depot before generalized spread Rarely are supraclavicular nodes involved if the aulla is negative and only the internal mammary nodes are positive The level of aulla involved, whether at the base the apex, has no bearing on internal mammary involvement 12 Direction of lymphatic flow is greatly influenced by the position of the primary lesion in the breast and the presence of spread to the aulle Handley look biopsies of the internal mammary nodes at the time of surgery and found mvokement in nearly one-third of all cases When the avllary nodes were positive, the internal mammary nodes were involved in 74 per cent of lesions in the media (91) 17 Or ·Estonded Radical Mastectomy 95 por cont Even half of the breast and 33 per cent of lesions in the lateral quadrants when the axilla was free of disease, the internal mammary nodes were positie in 8 per cent of cases The frequency of internal mammary nodo involvement has been cxpressed by others 3:14 When preliminary biopsy reveals involvement of pamsternal, supraclavicular or even highest adllary nodes, it is sometimes considered a contra indication to surgery. This attitude has been challenged, and final evaluation awaits the results of extended radical mastectomies or intelligently applied radiation therapy designed to encompass these areas Alargottini" in 1948 was first to attach the internal mammary nodes routinely In addition to a ndical mastectom; he divides the costal cartilages of the upper four ribs and removes the intemal mammary nodes and vessels along with the costal cartilages in an extrapleural manner Supraclavicular dissection is done at a later stage. Dahl Iversen reported 376 extended radical mastectomles includ ng & supraclavicular and paresternal dissection The costal cartilages were divided and the Internal mammary vessels were clissected off extrapleurally along with nodes The latter was not in continuity Mortality rate was below 1 In 20 per cent of cases internal mammary nodes were posithe Wangensteen 17 and recently Noelto have combined a radical mastectomy with removal of the internal mammary chain an anterior mediastinal dissection and a supraclavicular dissection m one or tivo stages The overall mortality has been significant Over one-half of cases were found to have involved nodes in pamsternal or supraclavicular areas which could not have been removed by a conventional radical mastectomy In an effort to extend conventional therapy to include the internal mammary chain without greatly increasing morbidity or mortality Urban" combined the radical mastectomy with an en bloc removal of the internal mammary nodes, vessels and chest wall from the first to the fifth interspices The resulting defect was closed with fascia lata In 300 cases16 mortality is less than 1 per cent and morbidity is only slightly increased. Hospitalization is not prolonged Post the internal mammary nodes were found in 35 6 per cent of theso patients and allar nodes in 47 6 per cent. Lesions in the medial half of the breast had involvement of internal mammary nodes in 60 per cent when the axilla was positive whilo with lateral quadrant lesions internal mammary podes were involved m 40 per cent of cases ! In 14 per cent, the internal mammary nodos were involved with tumor while acilary nodes were not. Hnndley? now includes extrapleural removal of Internal mammary nodes utilizing the pectoralls major for closure of the chest wall defect In 40 per cent of cases Internal mammarv nodes were positive Sugarhaler" found 52 per cent of merial qundant and subareolar cancers to have positie internal mamman nocles Ariel' described a more conservative en bloc resection of pansternal noules with priman repair of the chest wall defect The ultimate in radical ·96 Extended Radical Mastectomy surgery for breast cancer is descubed by Pıudente?) who has done 6 interscapulothoracic amputations for extensive disease. It has been well documented that internal mammary nodes are involved in the majority of inner quadrant cancers and in subareolar carcinomas of the breast when the axılla is positive 5,14 Since the axılla is involved in about 50 pei cent of all cases, an operative procedure which attacks the aulla but which Ignores the internal mammary nodes lacks some justification Extension of surgery to encompass this area must, therefore, include complete iemoval of the breast and axıllary contents as well as an en bloc resection of the internal mammary nodes, perforating veins and lymphatics This must be accomplished without any undue increase in mortality and morbidity Finally, this must add to the curability of the cancer The Urban procedure appears to fulfill these demands. Although early results indicate that the cure rate will be increased, more time is needed before complete evaluation of results is available Surgical Technique margin The The patient is draped in a supine position with the arm extended at right angles from the body (Plate 1) The opposite thigh is prepared for removal of a fascia lata graft A vertical incision is most commonly employed (Plate 28) extending from the clavicle to the subcostal margin encompassing the tumor by at least 10 cm with upper quadrant lesions. A triangular type incision is made sometimes and subsequent closure is facilitated by suturing the ski in a “Y” shaped manner Thun skin flaps are elevated to the opposite border of the sternum medially, to the border of the latissimus dorsi laterally, superio1 ly to the clavicle and inferiorly to the subcostal upper portion of rectus abdommis fascia is includca in the specimen The pectoralis is then split between its costal and clavicular attachments, preserving the latter The origin of the pectoralis is cleared off the fifth interspace just lateral to the sternal boider After carefully splitting the intercostal muscles of the first interspace, the internal mammary and intercostal vessels are identified and ligated Palpation at the base of the neck is made to detect any node involvement If present the procedure is discontimed as the disease would probably be generalized If none is found the fifth interspace is entered and the internal mammary vessels agu ligated list above the sixth rib (Plate 40) After demarcating the line of resection on the sternum, « Lichsche sterul splitting knife is inserted in the first interspace, and the stermuni split vertically between medial and lateral thirds down to the fifth mterspace (Plate 10). The pectoralis major is undermined lateral to its attachment on the chest wall, thaus e posing the costal cartilages of the second, third, fourth and fifth rilis, Thescartılages and mtercostal muscles are divided, and the flap of sternum and attached chondral segments of ribs with pectoralis major still attached is reflected bach-

·Extended Radical Mastoclomy
97
PLATE 40
Deltoid m
Clavicular portion, pectoralis major
Poctoralis minor
Pectoralis major
Clavicle
Corocotrochrols
1st rib
Sternum
Ponietal
pleura
Lung
Internal
mommary
orv
Rectus abdominis
Rectus sheath
7

·96 Extended Radical Mastectomy surgery for breast cancer is described by Prudentell, thoracic amputations for extensive disease It has been well documented that internal mamma majority of inner quadrant cancers and in subareol when the axılla is positive 5,14 Since the axılla is in of all cases, an operative procedure which attacks i the internal mammary nodes lacks some justificatio encompass this area must, therefore, include comple axıllary contents as well as an en bloc resection of t perforating veins and lymphatics This must be undue increase in mortality and morbidity. Finally, ity of the cancer The Urban procedure appears to fu early results indicate that the cure rate will be inc before complete evaluation of results is available Surgical Technique The patient is draped in a supine position with angles from the body (Plate 1) The opposite thigh fascia lata graft A vertical incision is most com extending from the clavicle to the subcostal mare by at least 10 cm with upper quadrant lesions is made sometimes and subsequent closure is facılık a “Y” shaped manner Thin skin flaps are elevated to the opposite borde the border of the latissimus dorsi laterally, superiorly to the subcostal margin The upper portion of rectu in the specimen. The pectoralis is then split betur attachments, preserving the latter The origin of th fifth interspace just lateral to the sternal border intercostal muscles of the first interspace, the inter: vessels are identified and ligated Palpation at th: to detect any node involvement If present the as the disease would probably be generalized If space is entered and the internal mammary vessels sixth rib (Plate 40) After demarcating the line of resection on the splitting knife is inserted in the first interspace, an between medial and lateral thirds down to the fift pectoralis major is undermined lateral to its attac} eyposing the costal cartılages of the second, thurd, fr tulages and intercostal muscles are divided, and the chondral segments of ribs with pectoralis major si

·Ertended Radical Mastectomy
90
PLATE 41
Brachiol plexus
Pectoralis minor
Axıllary arv
Lotissimus
dorsi
Fascia lata
closing defect
Subscapularis TY?)
Thoracodorsal n
Long thoracic n

·100 Extended Radical Mastectomy - ܚܝ 1 1 je Fig 11 – The skin edges are approvmated and cotton bolsters used to prevent dead space and fluid collection beneath flaps The chest tube is connected to under water drainage fifth postoperative day and again two days later The patient is discharged bctween the seventh to ninth day after surgery If a fascia lata graft was taken from the patient, Penrose drains in this area are removed on the third day, and firm pressure is maintained for several days following. Arm exercises are begun soon after surgery Function is the same as following a conventional radical mastectomy There is no impairment of respiration as a result of chest wall resection, and the cosmetic appearance is essentially the same as that following a radical mastectomy As yet, the final results pertaining to the eſlicacy of the citende procedure have not been completely defined (sec chapter on Results of Surgery, p 88, also p 63) Whether the internal mammary nodes constitute a sufficient filtering bed for a time to prevent generalization of cancer cells is not known. Removing the internal mammary nodes does not attack supraclavicular spread However, when supraclavicular nodes are involved the discase is probably beyond surgical removal 3.17 Radical mastectomy with chest wall resection will find ils greatest application u carly lesions that are centrally located or in the media hur of the breast Increase in cure rate is doubtful if there is massive involvement of either the ·Extended Radical Mastectomy 101 axdilla or internal mammary chain of Dodes Whether surgery or radiation, alono or m combination will be the most effective method to attack internal mammary nodes remains to be seen. Complimentary radiation therapy should be given to the base of the neck if nodes in the first interspace or npes of the axilla are positive It should never bo used as a substitute for adequate surgery By careful selection of patients a 5 to 10 per cent increase in results may be possible with the entended procedure in patients who ordinarily would not survive with radical mastectomy alone. BIBLIOGRAPHY 1 ARIEL, I M A Conscivative Mothod of Resecting the Internal Manmery Lymph Node En Bloo With Radical Vostectomy Surg., Gynec. & Obst., 100 623, 19.55 2. DAHL IVERSEN E. Recherches sur les metastases microscopiques des ganglions lytophatiques parastomaux dans le cancer du sein J intemat chir, 11 492, 1951 3 Extended Radical Operation for Dammary Cancer Third National Cancer Conference Proceedings Philadelphia, J B Lippincott Co p 148 1957 4 HAAGENSEN CD Diseases of the Breast Philadelphia, WB Sowders Co 1956 5 HANDLET RS Furthor Observations on the Internal Mammary Lymph Chain in Carcinome of the Breast, Proc. Roy Soc. Vled, 45 585 1952 B HANDLEY RS and TILACIRAY AC Invasion of Internal Mammary Lymph Nodes in Carcinoma of tho Breast, Brit A1 J., 1 61 1954 7 HANDLEY RS PATEY D H., and HAND BH Excision of the Internal Vammary Chain fr Radioul Mastectomy Lancet 1 457 1956 8 MAGGUTTIE M M Now Criteria for Operability in Breast Carcinoma Third National Cancer Conference Proceedings Philadelphie, J B Lippincott Co P 122, 1957 9 MARCOTTINT, MI The Surgical Treatment of Carcinoma of the Broast Coll. International do Chirurgiens, Volumes des rapports publice loccasion da XX Anniversaire 744, Gonove 1955 10 Norr, OF Extended Operation for Carctroma of the Breast, Surgery 38 423, 1935 11 PRUDENTE, A. Lamputation inter-scapulo-mammo-thoracque, į do chir, 65 729 1019 12. STEWART F IV Foctors Influencing the Curability of Cancer Third National Cancor Conforence Proceedings Philadelphia, J B Lippincott Co., P 62. 1957 13 STIBBE, E P: The Internal Mammary Lymphatic Glands J Anat., 53 257 1918 14 URBAN ) and BAGER, H 1 Radical Viastectomy in Continuity with En Bloc Resection of the Internal Mommary Chain, Cancer 3 992, 1952. 15 UNBAN JA Radical Vastectomy with En Bloc In Continuity Resection of the Internal Vammary Lymph Node Chair, Surg Clin N America, 1065 1956 16. Personal communication 17 WANGENSTEER O H LUWII, F and AHAELGER, SW The Extended or Super Radical Vestectomy for Carcinoma of the Breast, Surg. Clin N America, 1051 1956. 18 11 TATT J P SUGARBAIER, E D, and STANTOY V Involvement of Internal Mammar, Nodes in Carcinoma of Breast, Am J Path 31 143 1955 ·Chapter 9 RADIOTHERAPY OF BREAST CANCER noma RADIOTHERAPY has become an integral part of the treatment of mammary carci- At least half of the patients so afflicted will receive radiotherapy at some time in the course of their disease One challenge that confronts the physician interested in treating breast carcinoma is to define clearly the role of radiation used either as a primary therapeutic weapon or conjointly with various surgical procedures There are individual differences, but in general, the role of radiation in the treatment of breast carcinoma is supplementary to surgery PHYSICAL CONSIDERATIONS OF RADIATION RELEVANT TO BREAST CANCER Ionizing radiation is the term collectively applied to certam rays and fast particles which are capable of producing ionization by displacing orbital electrons from atoms with which they collide X-rays and gamma rays are of primary interest, since particulate radiations are infrequently used in treatment The unit of measurement most commonly used for 2-1 ays and gamma rays is the roentgen (r), defined in terms of the amount of ionization produced in allr. Dosage has been generally expressed as “roentgens in ar” but a more definitive and informative figure is the absorbed dose at the tissue or tumor, for which a new unit, the “rad," has recently been introduced and defined as an absorbed dose of 100 ergs per gram of tissue Low kilovolt x-rays (less than 140 kvp) evert their maximum biologic effect on the shin and immediately subcutancous tissues because of their relatively long wave length As the kilovoltage is increased there is an increasing penetrability, and thus, a greater relative amount of ionization reaches the tissues below the surface At the present time 200 to 250 hilovolt 1-rays aic most commonly i'mployed in decp r-ray therapy Supervoltage r-rays are produced at peak energies range of I to million volts Their major advantage lies in their ability to deliver a relatively large depth dose compared to the surface dose At the higher energy ranges millimum comzation takes place below the surface, and thus the shin is spread (Fig 12) in the (02) ·103 Radiothorapy of Breart Cancer 200 Kilovolts 50 com Target Skin Distance 10 X 10 an Field Slzo 4000 Klovolts (4 Mol) 100 cme Target Skn Distance 10 x 10 cm. Field Stzo 100 H00 0 ON re om 80 70 70 10 con 10 cm 30110 2010 Isto troca Loon zh a 125 0. 25 Fia, 12.-Comparison of irodose curves obtained with 200 Wlovolt and 4000 Wlovolt (4MeV) Σ ΤΟΥΣ, Gunma mys cmitted by radium and certain radioactive isotopes (Cobaltas) are being used more frequently now as teletherapy sources For practical purposes they can be considered as having essentially the mme lonization charac teristics as supervoltnge I rays BIOLOGIC CONSIDERATIONS OF IRRADIATION OF BREAST CANCER The cxact physical and chemical mechanisms nvolved in producing radiation injury in cells and tissues are unknown Hovever on the basis of numerous investigations, ranging from irradiation of unicellular organisms to hunan malignancies, several modes of cellular damage have been described it has long been known that cells which divide are more likely to shory evidence of madla tfon damage than cells that are mature and incapable of further division. It is on the basis of this fundamental observation that radiotherapy has been applicd to malignant neoplasms, since tho mitotic rate of eich growth tends to be greater than that of their surrounding normal tissues Radiation injury at the cellular level is manifested by (1) a failure of the cell to divide, with subsequent lysis ·104 Radiotherapy of Breast Cancer peroxides or giant cell formation and ultimate cell death, (2) abnormal mitotic cycle, manifested by delay in entering mitosis, prolongation of mitosis, particularly m prophase, chromosome aberrations with “stickiness,” and multipolar, frequently nonviable divisions, (3) genetic damage manifested by delayed cell death or abnormal development after a varying number of mitotic divisions The above observations are presumably due to an alteration in the desoxyribonucleic acid component of the nucleus of sufficient magnitude that the cell linc cannot propagate Recently, interest has centered on the role of oxygen on the biologic eſſect of radiation The present theory is that oxygen is necessary to convert short lived radicals to more efficient Although further basic research into this reaction is needed, the clinical implications of the oxygen effect deserve comment If a tumor has a poor blood supply, as is frequently the case in zones which are necrotic, the cellular oxygen level is insufficient to allow development of the maumum radiation reaction This may in part explain the relative msensitivity to radiation of large solid or fungating tumors It is suggested that if mavmum oxygenation at the cellular level could be physiologically obtained, radiosensitivity would be enhanced with a corresponding increase in the radiocu ability of the tumor At the tissue or organ level, radiation effects are obsei ved as the cumulative injuries of the myriad of irradiated cells This is manifested by altered physiology of the organ or organs involved Of particular importance in radiation therapy of cancer is the alteration of the blood supply by the effect of irraduation on the endothelium of capıllaries, small arterioles and venules This effect secondarıly impairs the growth potential of the tissue involved, probably by virtue of anovia and an insufficient nutritional supply to meet the demands of the tissue Alteration of the connective tissue stroma and blood vessels undoubtedly plays an important role in the final destruction or inactivation of Irradiated tumors Fractionation, or the division of the total amount of radiation given over al specified period of time, is based on the clinical finding that normal tissues are capable of recovering from radiation injury when the dose is given in relatively small increments In contrast to this, most malignant tumors are incapable of such rapid recovery from radiation injury, and thus a differential is developed By careful cyploitation of this differential rate of recovery, radiotherapists have been able to deliver cancericidal dosages mto malignant tumors with a minimum of permanent radiation injury to the adjacent normal tissues The optimum time dose relationship vanes with the clinical problem, but an average cancericulul lunor dose is 5000 to 6000 r delivered in live to sit wecks Jomizing radiations are capable of causing cellular changes m breast carcinom., but the question that remains is whether irradiation can completely crachute the carcinomatons tissue without irreparably damaging adjacent normal tissuie plus problem has been studied by miny investigators in an attempt to decide non ·Radiotherapy of Brerut Cancer 105 an optimal time-dose relationship Of great importance in cvaluating the results of irradiation of breast carcinoma is the knowledge that this disease is fofinitely variable in its biologic growth characteristics The histology varies widely from Bloom' patient to patient and even at times within the primary tumor itself correlated histologic grading with clinical staging and demonstrated that the Alve-year survival rate will vary within the clinical staging depending upon the grade of malignancy Taylors and Watson also found that the five-year survival rate was lower m patients who had breast carcinoma with a high grade of malignancy as determined by histology The role of the tumor stroma, hormonal infuence, and normal tissue resistance must be assessed to fully approdate the effect of irradiation on breast carcinoma Lumbat carefully studied the effect of histology with 200 Wlovolt x rays on 60 cases of breast aucinoma treated at "Vestminster Hospital, London The dosage administered ranged from 2000 to 4000 r given in tiventy to forty days Ho found (1) acute cell dissolution (2) altoration of cell structure with nuclear pyknosis, vacuoltzation in tho cytoplası giant cells and subsequent calcification (3) connective tissue changes with obliteration of small blood vessels and re placement of tumor areas with strands of acellular material These changes were not present in all cases, and he found po remaining cancer cells in only 7 out of 60 cases 4 of which were nmong the 11 cases receiving the madmum dose of 3500 to 4000 r His conclusion was that a dosago of 3500 to 4000 r is the minimum effective tumor dose. He found that he could not rely on histologic criteria to determmo which carcinoma would respond to a lower tumor dose Lenzio reported that the mastectomy specimens in all 38 patients given a tumor dose of 4500 r to one month roscaled microscopic persistence of ancer cells Williams reported on 18 cases initially inoperable and ghen preoperative irradi ation after biopsy Slicroscopic evidence of viable carcinoma was found in 17 of the 18 cases. The case in which no viable arcinoma was found was 1 of 4 treated with supervoltage (1 mev) i rays to a total tumor dose of 4500 r in thirty days The other 14 reported cases were treated with 250 kilovolts rays to an estimated tumor dose of 3000 to 3000 r in twenty-eight days Surgery was performed on these patients from four weeks to eighteen months later Williams also notes that 4 of 9 cases with positive adllary nodes preoperatively had persistence of the carcinoma in the podes removed at operation Williamsd cites 18 other advanced cuses treated by Ross and Boyd with I rays at a half value layer of I to 1,5 mm Cu up to a tumor dose of 3000 to 3500 run twenty-ono days All of these cases shorved microscopic evidence of vrable carcinoma cells in the primary tumor after mastectomy In 13 cases in which axillary dissection was performed positive nodes were found in 12 despite a tumor dose of 3000 to 3500 Baclasse described in detail his method of preoperative roentgen therapy followed by a mdical mastectomny Set cnty seven cases were treated in this manner from 1935 to 1956 Dosages vried from 4500 to 9000 r in a period ranging froin ten to sixteen weeks At no time was a severe skin reaction ·106 Radiotherapy of Breast Cancer allowed to develop, the maximum reaction noted was a diy desquamation Of the 77 cases, 9 were found to have no demonstrable carcmoma cells in the primary, but only 1 of the 9 cases with the primary "sterilized' had 110 viablo cancer cells in the axillary nodes. Irradiation as given by these investigators proved inadequate for complete eradication of breast carcinoma in the majority of patients However, viability is a difficult microscopic interpretation, particularly if the specimen is examined relatively soon after the irradiation Possibly irradiation induces m many breast carcinomas a period of dormancy, and therefore relative control without eradication THE REGIONAL SPREAD OF BREAST CANCER Halsted realzed that breast carcinoma metastasized not only to the avillan group of nodes, but also to the internal and supraclavicular chains Handley' rekindled interest in the problem of early spread to the internal mammary cham It was his discovery that the internal mammary nodes are involved 3 times as frequently with inner quadrant tumors as with outer quadrant tumors, that has stimulated surgeons to re-evaluate the classical Halsted adıcal mastectomy Handley14 also pointed out the increase in internal mammary cham involvement when the aulla is involved regardless of primary site, though agam inner quadrant tumors have a higher percentage when compared to outer quadrant tumors (Table 2) Table 2-Sites of Microscopic Metastases in Carcinoma of the Breast All nolce free Internal mammaril nocy alonc .frillary 101lcy alone Number of cስ የምያ brillarul and 13 MINITI nolce futhor 10 Handle (1950, 1950) Watt (1977) Dall-liersen (1971, 1951) Margottini (1918) Ilulahuinon (1849) 1. 199 60) 173 110 81 39 02 82 11 38 37 10 11 8 09 ،ر ا Dahl-Iversen initiated several series of cytended radical mastectomic's for breast carcmoma with the aim of finding out how often the ordmarı radical operation failed because of supraclavicular or internal mammary nocle melushorses The sites of metastases in lus fourth series are presented in Table 3 11 a series of extended radical mastectomies, confirmed Lundby's finding that the site of the primary and qullary nodo involvement are pranont factors in determimg internal mammary node involvement Haagensen," se confirmed the greater likchhood of mternal mammary node metastases when the primary ·Radiotherapy of Breast Cancer 107 tumor is in the medial or central portions of the breast Hutchinson17 and Margottini were unable to confirm Handleys finding regarding an increased frequency of internal maminary nodo metastases with moer quadrant tumors but did find that approdmately 20 per cent of patients with aullary node metastases did have lovolvomont of the internal mammary nodes at the time of radical mastectory Tablo 3-Sites of Blicroscopic Metastatos and Primary Groicth in 100 cases of Carcinoma of the Breast (Andreasen, Dahl Icetson and Sorenson, Courtesy of Lancet 1954) Site of primary goatk Sum of seaward Jadual Lateral + 21 0 Alry only l'internal only Lillary and panttertul lary and supraclavular lo metastas 7 0 3 Total 57 Suprclavicular metastases are found only in patients with axillary metastases The incidence of these podal metastases is lower than that of internal mammary node metastases, presumably because they occur at a later stage. Dahl Ivensen found supraclavicular metastases in 7 to 33 per cent of cases with axillary involve ment. This variation is apparently dependent upon differences in the clinical material available for his series The size of the primary carcinoma and the incidence of anllary metastases have a positive correlation, and this is presumably true for interni maomary Dode metastases as well The critical diameter at which the majority of breast cardnomas will metastasize is unknown, but vanous observers believe it is between 2 and 4 cm Robbms found axillary metastases in 395 per cent of cases with a prmary less than 2 cm in diameter compared to 74 per cent when the primary was 4 cm. or over Haagenseno concurs that most large carcinomas havo metastasized when the patient is first examined, and reports a 777 per cent incidence of axillary metastases when the primary is 7 con or larger From the foregoing revlev two conclusions can be drawn The site and size of the primary aurcinoma ju the breast determines the frequency and direction of metastatic spread to the regional lymph nodes As the degreo of aullar, nodo fuvolvement increases metastatic discase will be found more frequently in the Internal mammary and supraclavicular nodes ·106 Radiotherapy of Breast Cancer allowed to develop, the maximum reaction noted was a dry desquamation Of the 77 cases, 9 were found to have no demonstrable carcinoma cells in the primary, but only 1 of the 9 cases with the primary “sterilized" had no vable cancer cells in the axillary nodes Irradiation as given by these investigators proved inadequate for completo eradication of breast carcinoma in the majonty of patients However, vability is a difficult microscopic interpretation, particularly if the specimen is eammed relatively soon after the irradiation Possibly irradiation induces in many breast carcinomas a period of dormancy, and therefore relative control without eradication THE REGIONAL SPREAD OF BREAST CANCER Halsted realzed that breast carcinoma metastasized not only to the dullary group of nodes, but also to the internal and supraclavicular chains Handler i rekindled interest in the problem of early spread to the internal mammary chain It was his discovers that the internal mammary nodes arc involved 3 times as frequenth with inner quadrant tumors as with outer quadrant tumors, that lies stimulated surgeons to re-evaluate the classical Halsted radical mastectomy Handley li also pointed out the increase in internal mammary chain involvement when the aulla is involved regardless of primary site, though again inner quadrant tumors have a higher percentage when compared to outer quadrant tumors (Table 2) Table 2-Sites of Microscopic Metastases in Carcinoma of the Breast Inirenal DOMINOTY notor alone frillar amil rigrinultri ,1nillary noler alone noir lumur of coxca uthor Ilanoli11950 1956) 1. 22 199 IG 7 6 2 Halstern 1971 1974) Virgotteilla lluirlun in 1931 15? 110 SI 39 Touche u Dahl-Isessen mituted sucral series of estended radical unustactusmea for breast carcinoma with the aim of finding out liou often the ordin operation failed because of supraclavicular or internal mamınır not in tist!! Il sites of metastases m luis fourth series are presented in Table 1 111 of 11111s of riteuclid radical mastectomics confirmed Lundless find this! the sile of the primar and ulicr node isolument ure poruount fut?","> un vle it rouminosite su muminary nodemokumont H..nile criter! the are 180 g libelohors of internal inammin nude metastaseos a buen the printing ·Radiotherapy of Breast Cancer 107 tumor is in the medial or centru portions of the breast Hutcunson17 and Morgottini) nere unable to confirm Handlc s Anding regardmg an increased frequency of internal mammary node metastases with inper quadrant tumors, but did find that approximately 20 per cent of patients with anllarpode metastases did have involvement of the internal mammary nodes at the time of radical mastectomy Tablo 3 --Sites of Alicroscopic Metastares and Primary Grouth in 100 cases of Corcinoma of the Breast (Andreaxen, Dahl Icersen and Sonneen, Courtesy of Loncet, 1954) Site of primary grorth Sue of acader Vedral Lateral 4 + hry onlr Parustethul on Idlers and parternal Aulbars and rapidavicular To metastas 21 0 6 3 0 Toul Supraclavicular metastases are found only in patients with axillary metastases The mcidence of these podal metastases is lower than that of internal mammary node metastases, presumably because they occur at a later stage Dahl Iversen found supraclavicular metastases 10 7 to 33 per cent of cases with axıllary involvement. This variation is apparently dependent upon differences in the clinical Inaterial available for his series. The size of the primary carcinoma and the incidence of axillary metastases have a positivo correlation, and this is presumably true for internal mammary nodo metastases as well The crital diameter at wbich the majority of breast cardiomas will metastasize is unknown, but various observers believe it is between 2 and 4 cm Robbins28 found axillary metastases in 39.5 per cent of cases with a primary less than 2 con in diameter compared to 74 per cent when the primary was 4 cm. or over Haagensen!' concurs that most large carcinomas have metastasized when the patient is first examined, and reports 1 77 7 incidence of axillary metastases when the primary is 7 cm. or larger From the foregoing revietv two conclusions can be drawn The site and size of the primary carcinoma in the breast determines the frequency and direction of metastatic spread to the regional lymph nodes. As the degree of anllary node fnvolvement increases metastatic disease will be found more frequently in the internal mammary and supraclavicular nodes per cent ·108 Radiotherapy of Breast Cancer TREATMENT OF BREAST CANCER WITH IRRADIATION gave al tumor Preoperative Irradiation Although several European centers have advocated this technique for many years, it is no longer routinely employed in the United States Ash? presented the following points in favor of preoperative irradiation (1) ability of irradiation to destroy cancer cells, (2) effectiveness of post-irradiation fibrosis in devitalıing the cancer cell, (3) higher tumor dose possible, (4) normal tissues become less receptive to implantation, (5) devitalized cells spread by operative trauma are innocuous, (6) regression of an inoperable lesion may make surgical treatment possible, and (7) there is no delay in initiating treatment Ash' suggests that preoperative i-ray therapy should be given in all Stage III cases wherc. (1) the tumor is larger than 6 cm, (2) smaller than 6 cm with aullary nodes, (3) small tumor in medial quadrants showing retraction and aullary nodes Berven" used preoperative radiotherapy in all operable cases, and attempted to deliver a tumor dose of 2000 r to the breast and 1500 r to the axilla in 10 day's This was followed in three weeks by a radical operation, and then by postoperative irradiation given as soon as the wound healed Richardson dose of 3500 r to the breast and 1800 r to the aulla prior to radical mastectomy As evidence of its efficacy he reported a five-year survival rate m 15 Stage II cases of 66 per cent and in 52 Stage III cases of 39 per cent Baclesse reported on 77 cases given preoperative roentgen therapy No Stage I cases were included in the series He emphasizes that only a dry desquamation should be allowed to develop, and thereforc tahes up to ten wechs to deliver a 4000 r skin dose to lateral and medial tangential breast fields. The internal mammary cham is treated separately to a skin dosc of 6000 r The supraclavicular area is treated through a single triangular shaped field to a shin close of 4000 r if no nodes are palpable or to 7000 r of large nodes are noted the latter dosc may require four months to deliver With his techmque Baclesse has noted « 44 per cent five-year clinical cure rate The majority of those "cured are in carly Stage II Class Haagensen?" believes that clear-cut conclusions cannot be drawn from the s slable statistical data on the value of preoperative r-ray therapy for presents the following arguments against preoperative irradation (1) a mmmum tumor close of 500) r is necessary to arrest breast carcinoma and thus cannot safely 1x delacred to the primary tumor and regional node areas in less than sa nech, (2) surgers cannot be safely carried out until "racution reaction has subsecked, and thus, de limtive treatment is delayed for at least four months Preoperative irraduation should not be discarded without fur, somethi designed climeal trial utilizing their latest techmues of rachatierip deelnemers sequire the list of supervoltage traduction to the cluest wall, villa ܐܢ Sucks ·Radiotherapy of Breast Cancor 109 and supraclavicular arca. A tumor dose of 4500 to 5000 r could be given in four to five weeks, without the intonse skin renction seen with 200 Hlovolt I rays at this dose level Surgery could then be done six to eight weeks later with a minimal increase in surgical difficulties or complications Postoperative Irradiation Postoperative irradiation in breast cancer has wide appeal. It is based on the argument that mdiotherapy destroys any ancer remainmg after surgery and that possible avenues of spread, such as the supraclavicular foss and the pamsternal regions can be effectively sterilized X rays are generally used sinco the volume of tissue requiring irradiation annot be conveniently irradiated with radium Patients receiving postoperative roentgen therapy fall into three broad groups those that had their carcinoma ontiroly removed by surgery and in whom, therofore, the therapy is unnecessary those with undetected distant metastases at the time of surgery in whom the therapy cannot help and finally those with spread limited to the supraclavicular and ipsilateral internal mammary nodes who might be expected to benefit from such therapy Smithers' does not doubt that in cases with adllary node involvement post operative irradiation improves the survival mates Smithin a roview of breast carcinoma seen at Pondville, Massachusetts Hospital noted that 85 per cent with positive axillary nodes received supplementary I ray therapy He suggests that it is the supplementary I ray thempy that accounts for a freyer survival rate of 41 per cent as compared to 22 per cent for those cases with positive adlary nodes but do irradiation In addition he found an increased survival in those patients with Grade III tunors (based on a sale of IV) and negative anillary nodes receiving a ray therapy postoperatively as compared with thoso with similar tumors negative willary nodes and no i nay thempy Haagensen 10 does not use postoperative r nay therapy routinely preferring to reserve it for those patients who are found to have extensive adllary lovolvement As accuracy in the application of his strict criteria of operability11 13 has improved, relatively few patients are subjected to supplementary irradiation When it is given, a to portal technique, utilizing 2 mer I rays and coverlog only the supraclavicular fossa and pamsternal regions is employed. He offers Do figures as to relativo survival rates and the irradiation is given in the hope that may add to the patient s chance for cure The value of postoperative irradiation is difficult to define in a clear-cut foshion because of the multiplicity of factors that govem its usage either on a routine or individualized basis It is in patients who are expected to do poorly with Surgery alone that irradiation is advised, and thus survival rates may give an Croneous estimate of its value. The policy currently adopted at Stanford University Hospitals is based on the It ·110 Radiotherapy of Breast Cancer view that surgery, in properly selected cases, can effectively eradicate the disease in the breast and axilla, and therefore, routine postoperative 1-ray therapy in all patients is unnecessary In patients with (a) extensive aullary involiement, or (b) medial quadrant tumors, postoperative 1-ray therapy is given to the aper of the axilla, supraclavicular fossa and first three interspaces of the ipsılateral parasternal area For the supraclavicular field supervoltage at an energy level of 4 to 5 mey is used, whereas for the parasternal field we prefer to utilize 140 kilovolt 1-rays in an attempt to spare the deeper mediastinal structures from needless irradiation The parasternal field measures 6 x 9 cm and abuts the inferior margin of the supraclavicular field which has an average size of 10 x 12 cm (Fig 13). 又 Fic 13.-Portals used for postoperative irradiation Supervoltage 1-rays are insed for supraclavicular and aullary per arca 140 hilovolt i-rats are used for upper parasternal region Only the first three interspaces on thc ipsilateral side are treated Approve mately 30 per cent of internal mammary node metastases are located m the first three levels us our belief that if metastases are in the inconstant louer nodes or luave crossed the midlme the possibility that ſurther pread lias alreads occurred is too great to warrant radical therapy Morcover, since we atempt to deliver a minimum of 5000 r tumor dosc in four sechs to the parasternal artist, ·Radiotherapy of Brcast Cancer 111 the skin dose is about 7000 r and morbidity would be excessive ff a larger area of skin were treated to this dose level. A daily tumor dose of 200 nads is given to a total of 5000 rads for tho parasternal field, and a daily tumor dose of 225 rads is given to the supraclavicular fleld to a total of 5500 mds, in five weeks Only a mild skin reaction is noted in the supraclavicular field The pansternal field develops a brish epidermitis with desquamation of the shin, but subsequent heal fog occurs in six to eight weeks The resultant skin atrophy and telangiectasia are moderate if careful attention is given to skin care after treatment The chest well is not routinely treated. Primary Irradiation Therapy The patients generally submitted to this method of treatment are those that aro locally inoperable (acc Trentment of Inoperablo Cancer p 115) Lenz10 reported on 46 patients treated by radiation therapy alone Doses of 5500 to 8000 r were administered to the breast and avilla over a period of two to three months At the end of five years only 10 patients were alive and symptom free Watson't reported on all cascs of brcast carcinoma treated at the Cancer Clinics in Saskatchewan He divided his cases into three broad groups group I includes auses without known secondary nodes group includes those with secondary adliary nodes and group 3 includes all other cases Of the group 1 auses treated from 1932 to 1943 only 57 were given radiation alone and 52,6 per cent of these survived five years In group 2 cases there were 77 cases treated by radiation alone in the same time period and 22 1 per cent of these survived for five years In subsequent years "operable" cases wero rarely submitted to radiation therapy alone, and adequate dnta are not Available Baclesset treated 130 cases with irradiation alone but no Stage I cases were included in this series The dosage ranged from 4000 to 9000 r given over A protracted period, and the maximum skin reaction was a dry desquamation Forty-one cases (31.2 per cent) survived for a minimum of Ave years with the highest survival rate in cases receiving over 6000 r A major problem encountered with primary irradiation therapy is the marked skin reaction that occurs of tumor doses of 4000 to 5000 rare glven in five to six weeks with 200 kilovolt I rays Baclesset avoids this with exceptionally protracted therapy but most mdiotherapists believe the optimum time-dose relationship involves a tunor dose of 5000 r in five to six wechs The skin of the axilla is particularly sensitive to high doses of irradiation, possibly because of contact with other skin surfaces and maceration. The management of large areas of desquamation can be Very difficult. In some cases therapy must be discontinued before the desired tumor dose is given because of the severity of the skdn reaction The absence of severe skin reaction with supervoltage permits the delivery of a tumor dose of 5000 to 5500 r in flve to six weeks. The patients also have less

·112 Radiotherapy of Breast Cancer
systemic reaction to the irradiation and, therefore, tolerate the higher dosage.
Supervoltage 1-rays cannot be used in the treatment of the internal mamman
chain of nodes because of the high depth dose and injury to the underlying lung
and mediastinal structures Therefore, a compromise method must be used Such
a method utilizes supervoltage irradiation for the breast, chest wall, avlla and
supraclavicular areas, and lower voltage r-rays foi the upper parasternal arca
(Fig 14)
T
Juur
160
LATERAL
PORTAL
HEDIAL
PORTAL
FIG 14 - Portals used for primary irradiation of breast caremoina Supravoltage topols
are used for breast, „Ullary and supraclavicular arcas
140 hilovoll 1-r.11s re used for
pirusternal area
Tlie sodose pattern that supervoltage irradiation develops for the treatment of
the chest wall is seen in Figure 15 llare!" has developed a rotational s.mung
method using 3 mei 1-1,21'S

·Radiotherapy of Breast Cancer
113
MEDIAL
PORTAL
Intend money
ortory na
LATERAL
PORTAL
Fr. 15 - Irodose pattern obtained with supervoltage x rays in the treatment of
breast carcinoma
Simplo Mastectomy Plus X Ray Therapy
Tho employment of intensivo x ray therapy after simple mastectomy has been
espoused primarily by McWhirters 'He has treated the largest series of patients
by this technique, and reports a crude five year survival rate of 42 per cent in
1882 cases A simplo mustectomy is done to remove the primary tumor confirm
the diagnosis histologically and reduce the mass of tissue that must be irradinted
After healing of the wound intensive fractionated I ry therapy is given, utilizng
an I ray beam with a minimum half valuo layer of 37 mm Cu
To avoid a
severe reaction of the underlying pulmonary parenchyma tangential fields are
employed. The medial tnngential field border is placed 2 cm lateral to the
the uninvolved side m an attempt to irradiate the internal mammary
chain on the involved side
The axillary and supraclavicular chain of nodes is
Irradiated via two opposing fields, and a minimum tumor dose of 3750 r in three
vechs is considered a radical treatment with a madmum dose at any point
midline
of 4250 1
8

·114 Radiotherapy of Breast Cancer The main point in McWhirter's method of treatment is that simple mastectony and 2-ray therapy, given in his prescribed fashion, can be administered to $5 per cent of all cases of cancer of the breast, and thus offers a chance of cure to more patients McWhirter”” claims that at a maumum, only 14 per cent of all cases treated can be placed in a “disputable group” in which radical mastectomy alone might be equally or more effective than simple mastectomy and radiotherapy To facilitate the presentation of his data, McWhirter has divided lus cases into three groups as follows 1. Operable (Manchester Stage I and II) 2 Locally advanced (Manchester Stage III and approım appro\mately half of Stage IV) 3 Distant metastases (the remainder of Manchester Stage IV cases) With this classification his results are summarized in Table 4 Table 4. Results of Simple Mastectomy and Radiotherapy in the Treatment of Breast Cancer (McWhirter, Courtesy of Brit. J. Radiol., 1955). All Cases of Primary Breast Cancer Recorded 1911-17 Fire-year Crude Surriral Rate 1941-1? Trn-ycar C'rudr Surriral Rate Stage of Disease Total Vollre % Ihre Total No flere flere Operable locally advanced Distant molastases present 1003 576 273 619 162 19 58 30 f 971 157 09 99 23 () 39 17 () Total 1889 786 42 180 103 thi When it is realized that this series represents all patients presenting themselves for treatment, and is essentially unselected, the results are, indeed, satisfactory Ackerman? las evaluated this series and offers criticisms of the method lle cmphasizes the failure on McWhirter's part to present adequate histologic proof that 7-ray therapy in the dosage employed destroys nodal metastases In the few cases that did have follow-up biopsies of aullary nodes, active lumor grow was noted It may be that these were tumors with particularly aggressive grow thi characteristics Ilowever, though there is a spectrum of response 10 RCN dosage, VicWhirler' offers no proof beyond survival that the nodal melaslases were sterilized If in fact they were not, and only encasco 11 a fibrous scur, thus in time there wll be a recrudescence and dissemination thus mi account to some degree for Mellharter's less satisfactory ton-ycar crude surual rate of 35 ll is Vellhurler's clmcal impression that metastatic disease in the duilles better controlled by the treatment given than is the deschise 113 primint the breast Ilus vieu concurs with that of Leviti," ulo stated that online al Boules clue to carcinoma of the brcast are at least as rudiosensitive at the primus per cent ·Radiotherapy of Broast Cancer 115 It may and the end results are more permanent than in the primary growth Such a clafu may be true when expressed in relativo fashion, but dous not imply that all carcinoma of the breast metastatic to the axillary nodes is radiosensitivo be that a cancer can be controlled without eradicating all of its cells, and that the alteration by irraduation of cancer cells, or the tissues in which they lie brings about a dormant state adequate to control the cancer As the need arises McWhirter also uses other tools available to aid the breast cancer patient, such as hormones or ovarian sterilization Although this may confuse the evaluation of his series this practice cannot be condemned, and actually is found in many sugical series 13 The morbidity experienced by the patients undergoing this form of treatment annot be disinissed but is difficult to Assess. Achorman belleved that the morbidity was high and noted 47 serious postirradiation sequelae, including fmctured nbs and clavice In the final analysis VcWhirter sa contribution has been significant in that he has shown that breast cancer can be treated satisfactorily by means other than radical mastectomy Conceivably VcWhirters good results may be attributable to the avoidance of medical mastectomy per se rather than to his program of ndiation therapy The very early cases in which simple mastectomy was suff cient were not over treated and the equivocally operable cases had treatment adequate to control and restrain the disease without disseminntion as a result of infudidous radical surgery Objections can be made to NicWhirter 5* method of treating breast carcinoma A tumor dose of 3750 r in three weeks may be as efficient as a larger dosage over a more protracted period of time, but most investigators have found 3750 1 inadequate for the cradication of breast carcinoma in the majority of patients It is our belief that 5000 r in five weeks is the ininimuin tumor dose necessary to control effectively breast carcinoma McWhirter also does not present any todose patterns to substantinte his contention that the internal mammary chain of nodes is effectively treated by bus tangential fields The most serious error in McWhirter's work is that he has rigidly applied a singlo treatment method to a disease as variable as breast carcinoma Smce he failed to do a carefully controlled clinical trial, valid conclusions as to the merit of thus form of treatment cannot be drawn Inoperablo Cancer of the Brcant Tho primary method of treatment of patients with this situation is by irradiabon, but hormone therapy and simple mastectomy are added when indicated Thero are two broad groups those that are inoperablo becauso of regional spread, and those that are inoperable because of distant spread A Regionally inoperable A vigorous course of t my therapy as described previously (p 111) is warranted in these cases A stiple mastectomy can bo dono when the breast or primary tumor is of massive proportions and ·116 Radiotherapy of Breast Cancer radiation difficult Otherwise, surgery should be withheld Castration (surgical or x-ray) is performed on all patients having estrogenic activity as determined by vaginal smear examination Further hormonal measures are withheld until distant metastases require their use B Inoperable by virtue of distant metastases Roentgen therapy to the primary breast tumor is administered if ulceration is present or seems imminent Other areas are treated by irradiation as the clinical situation dictates, and only to palliation dose levels Simple mastectomy is rarely necessary Hormone treatment, such as, castration, the administration of androgens or estrogens, adrenalectomy or hypophysectomy are utilized as indicated Unusual Malignant Tumors of the Breast Non-epithelial tumors of the breast that exhibit malignant characteristics are rarely seen by the radiotherapist Many of these tumors are exceptionally radioresistant and radiotherapy is unwarranted In this In this group of radioresistant tumors are fibrosarcomas, liposarcomas, and malignant cystosarcoma phyllodes Surgery offers the only hope of cure in these patients. Hodgkin's disease has been reported to originate in the breast, but more often appears as a manifestation of generalized disease Similarly, lymphosarcomas and leukemia have been discovered in the breast The majority of these lesions respond to radiotherapy, although the patient eventually succumbs to spread of the disease If it can be shown that the tumor is limited to one breast radical mastectomy is the preferred method of treatment An alternative method is simple mastectomy and vigorous radiotherapy to the chest wall and lymph node drainage areas A tumor dose of 3000 r in three weeks to the involved areas is advised using 200 to 250 kilovolt x-rays PALLIATION OF BREAST CANCER BY IRRADIATION The palliative use of irradiation is undoubtedly its greatest contribution in the management of patients with advanced breast cancer. Nevertheless, cach patient must be carefully examined roentgenographically and physically, before treating, to establish the extent of the disease and the rapidity of its development To embark upon a vigorous course of palliative roentgen therapy without this knowledge may result in serious depletion of the patient's reserves Each case is individualized If the problem is one of local recurrence, and there is no evidence of spread, then a vigorous course of therapy is indicated As an caample, if the only manifestation of recurrence is a mass of supraclavicular nodes in a patient who is otherwise in good health, a long period of survival occasionally mav be obtained by initiating a course of x-ray therapy to the supraclavicular forssa and internal mammary chain of nodes A tumor dose of 4000 to 5000 rss GRO sithin a five-week period. The physical factors employed for the suprelo ·Radiotherapy of Breast Cancer J17 clavicular field are 200 to 250 kilovolts peak with a filter giving a half value layer of 1 mm of Cu and a target skin distance of 50 cm. If supervoltage therapy is available its use in the supraclavicular area is mdiented because of use af administration and relative comfort to the patient. Roentgen therapy offers a convenient and efficient method of dealiog with skin recurrences or skin metastases They are most frequently found on the chest wall but can be found in other areas. Physical factors utilized vary slightly depending on the thickness of the tumor but usually 100 to 140 Wlovolts peak, with a filter giving a half value layer of from 4 mm Al to 0.5 mm Cu, and a target skin distance of fram 25 to 50 cm, will suffice A field dze ndequate to cover the lesion with a moderate margin is used, and a tumor dose of 3500 to 4000 r is given in three and one half to four weeks If the field size is small (less than 50 sq cm) treatment can be given 3 times weekly at a rate of 400 r tumor dose per treatment If the area encompassed is larger daily treatments of 200 to 250 r tumor dose are advised to allow the normal tssues to recover Tangential fields are unnecessary for the treatment of mall recurrences on the chest wall with the lower kilo. voltages since tho attenuation of the I ray beam is suffiaent to prevent sorlons injury to the lung parenchyma. If the field is over 50 sq cm tangential fields are useful in proventing radiation pneumonitis Soft tissue metastases in sites other than the skin occur frequently in breast cancer and x ray therapy for them is warranted if symptoms arise Unilatern] pulmonary parenchymal metastases can be arrested temporarily often enough to encourage their treatment If supervoltage therapy is available parallel opposing portals accurately localized are used Only a small margin of normal tistue is Irraduated in order to prevent extensive pulmonary fibrosis A tumor dosage of 4500 to 5000 r in four to five weeks is given With 200 to 250 kilovolt a rays it is difficult to give dosages in this range without bringing on a moist desquama tion of the skin Therefore multiple fields are emploved to deliver tumor doses of 3500 to 4000 r in four weeks This will cause a moderate radiation pneumonitis and meticulous aro of the patient is necessary to provent serious complications Bilateral, pulmonary parenchymal, hular or pleural metastases are rarely relſeved with external x ray therapy Pleural metastases with a rapidly accumu lating effusion is helped by the instillation of radioactive colloidal gold or chemotherapeutic agents, such as nitrogen mustard or Thio-TEPA (see chapter on Chemotherapy P 125) Similarly visceral metastases do not respond well to roentgen therapy Ascites occasionally is helped by the instillation of radioactivo colloidal gold or chemotherapeutic agents Intestinal obstruction due to meta strses must be corrected surgically Brain or spinal cord metastases that can be accurately localized, preferably both clinically and roentgenographically are treated with I my with temporan benefit. They receive a tumor dose of 3000 to 3500 r in four to five weels Phys. ial factors aro 200 to 250 kilovolts peal, half value layer 1 to 2 mm Cu and a target skin distance of 50 cm The region involved is best irradiated through ·118 Radiotherapy of Breast Cancer opposing or oblique fields to avoid the moist skın reaction that occurs it only one field is used Bone metatases occur in over half the patients with breast carcinoma, and the majority of these metastases cause symptoms. It is in the relief of pain from these metastases that t-ray therapy is most often employed The vertebral column, pelvis, thoracic cage, skull and upper femora are commonly involved Considerable destruction of normal bone is necsssary before such metastases are detected roentgenographically The lesions are usually osteolytic, but can be osteoblastic or mixed Patients with obvious metastatic disease elsewhere, who have pain in a specific region but show negative roentgenograms, probably have metastatic involvement and treatment is given empirically Treatment of bone metastasis not only relieves pain, but will often prevent fractures or neurologic complications If multiple areas are involved care must be exercised to prevent undesirable radiation side effects due to the large volume of tissue being irradiated Physical factors of the r-ray beam generally used for the treatment of hone metastases are 200 to 250 kilovolts peak, half value layer of 1 to 2 mm Cu and a target-skin distance of 50 cm Portal size will vary with the situation encountered, but a severe skın reaction is to be avoided, and multiple oblique or opposing fields are necessary A daily tumor dose of 200 to 250 r is given to a total tumor dose of 2000 to 2500 r in two to three weeks This will bring relief of pain in about 60 to 75 per cent of patients and frequently many comfortable years of survival Re-ossification and recalcification of the involved area will often be demonstrable roentgenographically With a return of symptoms, the arca may be safely re-treated if the initial dosage was not above 3000 r The limiting factor is usually the skin reaction, but careful administration of the 2-ray therapy and meticulous care of the skin will allow re-treatment in most instances dosage of 2000 to 2500 r is desirable, but the treatment time can be extended if necessary to avoid moist desquamation Castration in women at the menopause or premenopausally has been used for many years as a means of altering hormonal activity and thus upsetting the tumor's dependence on estrogens The time to employ this tactic in the course of the disease has been a source of controversy and still is undecided This has been discussed in a previous chapter and a method of approach outlined (see p. 80) The finding that 2-ray castration is not permanent has caused many to turn to surgical castration Mere cessation of menses is not sufficient to insure suppression of ovarian estrogenic activity Patients undergoing roentgen castration should be checked for the development of typical castration patterns in their vaginal smears before the administered dose of r-rays is considered adequate It has been our policy to eradicate ovarian function with r-ray therapy by utilizing a graded dosage, depending upon estimated ovarian activity Patients who are in the menopanse or up to hve years postmenopausal receive an ovarian A tumor ·Radiotherapy of Breast Cancer 110 dosage of 1500 to 1800 r in tro and one-half weeks Patients who are approxi mately five years premenopausal receive an ovarlan dosage of 1800 to 2000 r in two and one-half weeks while thost more than five years premenopausal (utilizing age forty seven as the average age of onset of menopause) will be given 2000 to 2500 r in three wechs. The physical factors are 200 to 250 kilovolts peah, half value layer 1 to 3 mm of Cu, and 50 to 70 cm trget shin distance The field sizo usually measures 10 x 15 cm Opposing anterior and posterior portals are used giving between 150 to 200 r tumor dose per day (see Fig 18) FIG. 16 - Antelor portal used to i ry castration A parallel and opposing posterior portal is also used Side effects of irradiation, such as nauses, anorexia, cramping lover abdominal pam, and diarrhea are infrequently encountered, and tend to be minimal and translont Tho skin develops a moderate erythema which sometimes proceeds to a dry desquamation, and finally to minimal tanning A fall in the total white blood coumt, particularly of the lymphocytes will occur but this is not marhed. Menopausal symptoms are noted in six to eight weeks in the premenopausal patients, and can be managed with sedatives as required Obviously estrogens should not be given to relieve the menopausal symptoms BIBLIOGRAPHY 1 ACTERIAN LV An Evaluation of the Treatment of Cancer of the Breast at the University of Edinburgh (Scotland) under tho direction of Dr Robert Micly hirter Cancer 8 883 1955 2 ANDREASSEY 11., DAFL luz SEX E., und SONEXEY B Clandular Victastases in Carcinoma of the Breast, Lancet, 1 178 1954 ·120 Radiotherapy of Breast Cancer 9 3 Ash, C L, PETERS, V, and DELARUE, M. C The Argument for Preoperative Radiation in the Treatment of Breast Cancer, Surg., Gynec & Obst, 96, 509, 1953 4 BACLESSE, F Roentgen Therapy as the Sole Method of Treatment of Cancer of the Breast, Am J Roentgenol, 62, 311, 1949 5 A Method of Pre-operative Roentgentherapy by High Doses, Followed by Radical Operation for Carcinoma of the Breast, J Fac Radiol, 6, 145, 1955 6 BERVEN, E Treatment and Results in Cancer of the Breast, Am. J. Roentgenol, 62, 320, 1949 Ī BLOOM, H ) The Role of Histology in the Treatment of Breast Cancer, Brit ) Radiol, 29, 488, 1956 8. DAHL-IVERSEN, E Recherches sur les metastases microscopiques des ganglions lymphatiques parasternaux dans le cancer du sein, ) internat chir, 11, 492, 1951 Recherches sur les metastases microscopiques des cancers du sein dans les ganglions lymphatiques parasternaux et sus-claviculaires, mem Acad. de chir, 78, 651, 1956 10 HAAGENSEN, C D: Diseases of the Breast, Philadelphia, W. B. Saunders Co, PP 378, 584, 685, 1956 11 HAAGENSEN, CD, and STOUT, A P Carcinoma of the Breast, Criteria of Operability, Ann Surg, 118, 859 and 1032, 1943 12 Carcinoma of the Breast, Results of Treatment, 1935-1942, Ann Surg, 134, 151, 1951. 13 HANDLCY, RS, and THACKRAY, A C The Internal Mammary Lymph Chair in Carcinoma of the Breast, Lancet, 2, 276, 1949 14 Invasion of Internal Mammary Lymph Nodes in Carcinoma of the Breast, Brit MJ, 1, 61, 1954 15 HANDLCY, RS, PATCY, D H., and Hand, B H Excision of the Internal Mammary Chain in Radical Mastectomy, Lancet, 1, 457, 1956 16 HARE, H F, TRUMP, J G, and WEBSTER, E W' Rotational Scannmg of Breast Malignancies with Supervoltage Radiation, Am J Roentgenol, 68, 435, 1952. 17 HUTCHINSON, WB Intercostal Dissection and Radical Mastectomy, ANA Arch Surg , 66, 440, 1953 18 LENZ, M Tumor Dosage and Results in Roentgen Therapy of Cancer of the Breast, Am J Roentgenol, 56, 67, 1946 19 Radiocurability of Cancer, Am J Roentgenol, 67, 428, 1952 20 LEVITT, WM A Handbook of Radiothcrapy for Senior and Postgraduate Students, London, Harvey and Blythe, 1952 21 LUMB, G Changes in Carcinoma of the Breast Followmg Irradiation, Brit ). Surg , 38, 82, 1950 22 Mc\VHNTEN, R Simple Mastectomy and Radiotherapy in the Treatment of Breast Cancer, Brit | Radio), 28, 128, 1955 23 MARGOTTINI, M, and BUCALOSSI, P Le metastası linfoghandoları malinmarie interne nel cancro della mammella, Oncologra, 23(2), 70, 1949 24 PACK, GT Argument for Bilateral llastectomy, Editorial, Surgery, 29, 929, 1951 Carciona in 25 PILRCI, E H , KinkLix, J W, McDonali), ) R, and Garr, R P the Medial and Lateral Halves of the Brest, Surg., Gynee Obst, 103, 759, 1956 20 PRUDL1L, A Postoperative Prophylaws of Recurrent Mammari Ciucer with Testosterone Propionate, Surg., Gynec & Obst, 80, 575, 1943 27 RICHARDS, GE Mammary Cancer, the Place of Surgers and of Badutherapi 111 Ils Vanagement, Part 1, . Study of Some of the factors which Determine Success or Failure in Treatment, Brit J Radiol, 21, 109, 1918 ·Radiotherapy of Breast Cancer 121 28 ROBBINS GF, and BRASS Į The Significance of Delay in Relation to Prognosis of Patients with Primony Operablo Breast Cancer Cancer 10 338 1957 29 SADMIN M B LUCIA, E STOVE RS and BCLL, HC Cancer of Breast Analysus of Frequency Distribution and Mortality at Univerdty of California Hospital Surg Gynec & Obst H4 615 1952 30 SMITH, GV and Sum O IV Carcinoma of the Breast Results, Evaluation of irradiation and Relation of Ago and Surgical Costration to Length of Survival, Surg Gynec. & Obst., 97 508 1953 31 SIZ, DW., RIGB) JOVES P GALTON D A G., and PANE, PV Cancer of the Breest, Brit J Redol Supp. No 4, 1952 32 Tarlon, GW Treatment and Results in Cancer of the Breast Am J Roent genol, 62 341 1949 33 TREVES N An Evaluation of Prophylactic Castration in the Treatment of Alam mory Carcinoma, Cancer 10 393, 1957 31 URBAN JA Early Diagnosis of Breust Cancer Cancer 8 1173 1958 35 UAD AN J A, and BALER, J !! Radical Vestectomy in Continuity with En Bloc Resection of the Internal Alammaty Lymph-Node Chain, Cancer 5 992 1852. 38 WANGENTIZEN O J Proceedings of the Second Int Cancer Conf Cincinnati, 1 230 1952, 37 WATSON TA Results of Treatment of Cancer of the Breast, Surg Gynec. & Obst, 101 106 1957 38 WILLIAMS I G., and CUNNIN GILAN GJ Histological Changes in Irradiated Carcinoma of the Breast, Brt. J Racliol 24 123 1931 39 W TATT J P, SUCARBAIER, F D and STANTON VF Involvement of Internal Mammarv Lymph Nodes in Carcinoma of the Breast Am J Path 31 143 1955 ·Chapter 10 TREATMENT OF METASTATIC BREAST CANCER BY OOPHORECTOMY, HORMONES AND CHEMOTHERAPY 51 ALTHOUGH important advances have been made in the techniques of operative surgery and radiation therapy many women with mammary cancer ultimately develop disseminated metastatic disease The clinical course of mammary cancer, being extremely variable, permits a large proportion of women to survive for more than five years In the disseminated stage therapeutic emphasis shufts from an aggressive effort, directed toward cure, to a conservative and supportive approach where the goal of therapy is the relief of symptoms and distressing complications, and the prolongation of useful life Much can be done by the physician to assist individual patients from a medical and psychological standpoint Helpful palliative therapy of metastatic breast cancer is achieved by hormonal manipulation, and in certain instances, chemotherapy These methods are not curative and the results obtained are usually of limited duration and extent They produce only a moderate degree of objective tumor regression, but considerable subjective improvement is experienced by the patient In many instances hormonal agents produce serious and undesirable effects Their application, therefore, requires careful individualization and control The rationale of hormone therapy of breast cancer rests on the concept that some breast cancers retain the characteristics of normal breast tissue, particularly with respect to hormone control It has been empirically established that the progress of mammary carcinoma may often be favorably, although temporarily, affected by the administration of large doses of sex hormones or by the removal of the sources of endogenous hormone production by oophorectomy, adrenalectomy or hypophysectomy The response to hormone therapy is dependent upon the age and menopausal status of the patient, and the extent and nature of the metastatic involvement Treatment with hormones is indicated only in patients with disseminated metastatic disease Oophorectomy In the premenopausal and early menopausal patient with dissemmatod breast cancer, where it has not been possible to control local or metastalic lessons bv surgical and radiological means, the initial form of hormonal therapy los fue emploved is castration, preferably by surgery Oophorectomy produces objecte (2) ·Treatment of Dictastatic Breast Cancer 123 tumor regression in approudmately 20 per cent of patients • Evidence of tumor regression associated with this procedure usually occurs within six weeks, and its suppressive effect may last for six months to several years Castration by raduation may be as effective as by surgery but the results produced by surgery are more prompt and more certain Oophorectomy in postmenopausal patients is followed by little clinical response but is to be considered. Prophy lactic castration at the tune of the initial radical mastectomy or before the development of symptoms from metastatic disease has not been demonstrated to fncrease the curo rate or to prevent or delay conclusively the onset of mcta stuses (sec p 80) Its early use deprivos the patient of an important method of palliation at a later date 10 In the rarely seen male patient with carcinoma of the breast and disseminated metastases, orchicctomy offers a similar mesure of temporary palliation 11 Androgenic Hormoncs Androgenic hormones wero introduced in the treatment of advanced breast ancer with tho belief that estrogens are in some way implicated in the etiology or activation of breast cancer and thus androgens might bo espected to suppress brcast cancer This does occur but the mechanism of action of androgens in producing suppression of mammary cancer is not understood. Tho androgens are used as palliative agents at any stage of disseminated cancer and before or after the menopause They are employed in premenopausal patients with progressive metastatic disease following relapse or failure to respond to oophorectomy Subjective improvement charactorized by euphoria and relief of pain, occurs in 20 to 25 per cent of patients * 7 Approximately twothirds of patients with bone metastases experience relief from pain within one or two weeks after beginning therapy Soft tissue metastaser aro less responsive to androgens and regression occurs slowly Metastases in the liver and brain rarely respond The duration of androgen induced renissions is usually not over six to eight months, and seldom more than a year Treatment with androgen must be con tinued for ten to twelve wechs before its effect can be appraised. Occasionally a transient "Hare" or cracerbation of symptoms produced by the tumor mny precede the onset of a regression. Following response to therapy the androgen is continued unul a relapse occurs Often further tumor regression will follow discontinuation of therapy so that it is destrable to wait several weeks beforo employing other methods of therapy When relapse occurs m the premeno pausal patient after an adequate trial with androgen, adrenal steroids or surgical measures, such as adrenalectomy or hypophysectomy may be considered Androgen preparations and their dosage 1 Testosterone proprionate in oil, 100 mgm intramuscularly 3 times a wech. 2. Methyltestosterone 35 to 100 mgm orally dnily or 40 mgm sublingually daily ·124 Treatment of Metastatic Breast Cancer 1 3 Fluoxymesterone, 20 mgm orally, daily The last named is a new, potent androgen similar in effect to testosterone and having the advantage of oral administration Long acting androgenic preparations are not recommended since their effect persists for two weeks and they cannot be readıly discontinued if complications develop The clinical response with the androgens, though variable, has been better when given intramuscularly rather than by the oral route Unpleasant and distressing side effects of androgen therapy include vırılısm, hirsutism, deepening of the voice, acne, flushing, sodium retention, and increased libido Hypercalcemia, which occurs in approximately 10 per cent of patients with extensive osteolytic metastases, is significantly increased with androgen treatment Symptoms, which occur after several weeks or months of treatment, include drowsiness, unusual behavior, nausea and vomiting, constipation, polyuria, and ultimately coma and death It is necessary to evaluate the level of urinary or serum calcium at regular intervals during androgen therapy Hypercalcemia, which is accompanied by an increased urinary calcium excretion, is readily detected with the urinary Sulkowitch test A 3 or 4 plus reaction is indicative of increased calcium excretion and is confirmed by a serum calcium determination When patients develop evidence of hypercalcemia, prompt coriective measures are instituted These include withdrawal of the androgen, institution of a high fluid intake, ambulation when possible, removal from the diet of calcuum-rich foods, such as, milk and cheese, and the administration of large doses of adrenal steroids Cortisone acetate in initial doses of 300 to 400 mgm per day, or prednisone in doses of 60 to 100 mgm per day often produce dramatic clinical improvement and a decrease in serum calcium levels In these patients, resumption of androgen therapy is undertaken with caution Estrogenic Hormones Estrogens are employed in patients five years beyond the menopause They are also used in males with widespread breast cancer. Tumor regression with this form of therapy is surprising in view of the stimulating effect of estrogen on the tumors of premenopausal patients The palliative value of estrogens has been established by empirical use tis Large doses favorably produce objective regres. sions in soft tissue metastases and pulmonary metastases Ulcerated primary lesions may hcal Estrogens are less effective on osseous metastases and patients with liver metastases seldom respond Subjective improvement is esperienced by approvmately half of the patients treated The effect of estrogen therapy is usually cvident within one to three months It should be administered for at least three months before concludmg that the treatment is without wlue If the patient responds to therapy, estrogens is ·Treatment of Metastatic Breast Cancer 125 continued unul cvidenco of relapse occurs In the event of relapse the patient may be started on a trial of androgen therapy as described for the premenopausal patient Objective regressions produced by estrogens persist for slı to eight months, ocusionally longer Elderly patients have better response to estrogens than do younger postmenopausal patients Estrogen therapy should be started with caution in the latter group as treatment may occusionally produce an exacer bation of the cancer Estrogen preparations and their dosage 1 Ethmyl estradiol, 3 mgin orally daily 2 Diethylstilbesterol, 15 to 30 mgm orally daily Complications of estrogen therapy include sodium retention and edema, anoreda, nausea, vomiting, uterine bleeding, pigmentation of the nipples, and occasionally exacerbation of tumor growth. In most mstances pausea and vomiting are controlled by chlorpromazine administration in oral doses of 10 to 25 mgm., 3 times daily In elderly patients with heart disease sodium retention may precipitnte congestive heart failure Appropriate dietary sodium restriction and diuretics are employed, and careful supervision is maintained Uterine bleeding may be controlled by sharply increasing the dose of estrogen. Adrenal Steroid Hormones Administration of adrenal steroid hormones, cortisono prednisone, and pred nisolone, produces marked subjective Improvement in the form of euphoria, improvement of appetite, increased vigor and other manifestations. Unfortu nately they do not produce a significant degree of tumor regression and are best reserved for palliation of patients with far advanced disease who have received all above described methods of treatment. Dramatic relief of symptoms produced by cerebral metastases and by hypercalcemla may follow the administration of adrenal steroids They are also of occasional value in the treatment of hemolytic anemla accompanying breast cancer Complications of therapy with adrenal steroids includo Cushings syndrome, edema due to sodium retention, hyperten slon, diabetes peptic ulcer and psychosis Adrenal steroid preparations and their dosage 1 Cortisone ncetato 100 to 200 mgm orally daily 2. Prednisone, 40 to 100 mgm orally daily 3. Prednisolone 40 to 100 mgm orally daily Chemotherapy Systemic chemotherapy with currently available compounds is of littlo prac. Heal value in the majority of patients with far advanced breast cancer Temporary subjective improvement, and infrequent tumor regression have been ob- ·126 Treatment of Metastatic Breast Cancer 13 gauge needle served occasionally following the intravenous administration of nitrogen mustard Reports of benefit from the phosphoramide group of drugs have not been confirmed 2,12 At present, the most useful application of chemotherapy in the management of breast cancer is in the control of recurrent malignant pleural effusions and ascites The direct injection of nitrogen mustard into the involved cavity will eliminate or suppress an effusion in approximately two-thirds of the patients This method of control compares favorably with results obtained using radioactive gold or chromium phosphate It has the important advantage of being easily administered, readily available, inexpensive, and without radiation hazard The procedure is carried out as follows Approximately half of the pleural or ascitic fluid is withdrawn and nitrogen mustard is injected into the cavity. The dose employed is 04 mgm kg of body weight, amounting to a total dose of 20 to 30 mgm in the usual patient The solution is prepared immediately before administration, so as to avoid loss of potency through hydrolysis, and is dissolved in 50 cc. of normal salıne In patients with pleural eſfusions the drug is injected through the same needle used for thoracentesis, whereas in patients with ascites it is injected at a different site in the peritoneal cavity by means of a long, #22 Care is taken so that a free flow of fluid is obtained from the cavity before the drug is injected, assuring that it is not injected into the tissues Following injection of nitrogen mustard the patient is placed in a vanety of positions in order to distribute it throughout the pleural or abdommal cavity On the following day the remaining fluid is withdrawn from the body cavity Pain is seldom experienced following injection of nitrogen mustard into the pleural cavity, but pain, nausea, vomiting, and peritoneal irritation may be experienced for several days following its injection into the peritoncal cavily Nausea and vomiting usually are experienced within a few hours following administration of nitrogen mustard, but can be controlled with 25 mgm chlorpromazine, intramuscularly, given immediately before the procedure and at two hour intervals for 2 or 3 doses following the injection. Bone marron depression is mild with this method of administration, and repeated courses 'l he of nitrogen mustard are given at two or three week intervals if necessary hematologic status is watched carefully nonetheless Extra Caution should be employed in patients who hasc received cxtensive radiation therapy to bone metastases A suggested plan of therapy for dissemmated minimary circmoma is shown D] Tible 5 It is anticipates that many new and more effective synthetic androgen and estrogen derivatives will be made available withic mer future In addition, . clarification of the value of presently available hormones will result from the cooperatic research effort being conducted by the Vational Cancer Chemotherapy Service Center of the National Cancer Institute', nd a large group of cooperating medical schools" of ·Treatment of Bíetastatic Breast Cancer 127 Table 5 Postmenopausal Premenopausal or Early Wonopausal Bono Lettons Predominating 1 Androgen Soft Tiesto Predominating 1 Estrogen 1 Castration 2 Androgen 2 Estrogen 2 Anxirogen 3 Chalco of a Adrenal cortical starolds supportive b Ablatio surgery hypophysectomy adrenalectomy 6. Experimental chemotherapy-alkylating agcats antimotabolitos, oto. At any time during course of disease 1 Radiation tlicrapy for localized lesions 2 Mitrogen mustard, or radioacthe materials for intrucardtary infection for malignant effusions and oscites BIBLIOGRAPHY 1 BACCR, WH Abnormalities in Calcium Metabolism in Malignancy Effects of Hormono Therapy Am J Med, 21 714 1956 2 BATESIAN J C and CARLTOY HN Pallintion of Mammary Carcinoma with Phosphoramide Drugs J.A.MA 162 8 1056 3 ENDICOTT L M The Chomotherapy Program ] Nat Cancer Inst 19 275 1957 4. HUCCIN, C Endocrine Methods of Treatment of Cancer of the Breast, J Nnt Cancer Inst 15 1 1951 5 KENNEDY B I and NATTIA:VSOV I T Effect of Sex sterold Hormone Therapy In Advanced Breast Cancer JAMA 153 1135 1053 6 KENNEDY B J Fluoymesterono in the Treatment of Advancd Breast Cancer Cancer 10 813 1957 7 LEWTOY E F TADDLC, F H and GANTLIN R. S Advorced Mammary Cancer Treated with Sax Hormonos J.AMA, 162 1429 1956 8. NATTLAXBOY IT Clinical Investigate Experience with Sterold Horrones in Breast Cancer Cancer 5 751 1952 9 Stasy MB LUCIA, E L STOVE, RS and BELL HG Cancer of the Broast Analysis of Frequency Distribution, and Vlortality at the University of California Hospital 1918 to 1947 Inclusive Surg Gynec & Obst., 94 615 1952 ·126 Treatment of Metastatic Breast Cancer gauge needle served occasionally following the intravenous administration of nitrogen mustard Reports of benefit from the phosphoramide group of drugs have not been confirmed 2,12 At present, the most useful application of chemotherapy in the management of breast cancer is in the control of recurrent malignant pleural effusions and ascites The direct injection of nitrogen mustard into the involved cavity will eliminate or suppress an effusion in approumately two-thirds of the patients 13 This method of control compares favorably with results obtained using radioactive gold or chromium phosphate It has the important advantage of being easily administered, readily available, inexpensive, and without radiation hazard The procedure is carried out as follows Approvmately half of the pleural or ascitic fluid is withdrawn and nitrogen mustard is injected into the cavity. The dose employed is 04 mgm kg of body weight, amounting to a total dose of 20 to 30 mgm in the usual patient The solution is prepared immediately before administration, so as to avoid loss of potency through hydrolysis, and is dissolved in 50 cc of normal salıne In patients with pleural effusions the drug is injected through the same needle used for thoracentesis, whereas in patients with ascites it is injected at a different site in the peritoneal cavity by means of a long, #22 Care is taken so that a free flow of fluid is obtained from the cavity before the drug is injected, assuring that it is not injected into the tissues Following injection of nitrogen mustard the patient is placed in a variety of positions in order to distribute it throughout the pleural or abdominal cavity On the following day the remaining fluid is withdrawn from the body cavity Pain is seldom experienced following injection of nitrogen mustard into the pleural cavity, but pain, nausea, vomiting, and peritoneal irritation may be experienced for several days following its injection into the peritoncal cavity Nausea and vomiting usually are experienced within a few houis following administration of nitrogen mustard, but can be controlled with 25 mgm of chlorpromazine, intramuscularly, given immediately before the procedure and at two hour intervals for 2 or 3 doses following the injection Bone marrow depression is mild with this method of administration, and iepeated courses of nitrogen mustard are given at two or thiee week intervals if necessary The hematologic status is watched carefully nonetheless Extra caution should be employed in patients who have received extensive radiation therapy to bone metastases. A suggested plan of therapy for disseminated mammary carcinoma is shown in Table 5 It is anticipated that many new and more effective synthetic androgen and estiogen derivatives will be made available in the near future In addition, a clarification of the value of presently available hormones will result from the cooperative research effort being conducted by the National Cancer Chemotherapy Service Center of the National Cancer Institute, and a large gioup of cooperating medical schools 3 ·Treatment of Metastatic Breast Cancor 127 Table 5 Postmenopausal Premenopaural or Early Venopawel Soft Turun Bone Lerons Predominating 1 Androcon Predominating 1 Estrogen 1 Castration 2. Androgen 2. Estrogen 2. Androgen 3 Cholco of & Adrenal cortical sterolds-supportive b Ablativo airger-hypophysectomy adrenalectory c Experimental chemotherapy-alkylating agents antimetabolites, ctc. At any time during course of disease 1 Radiation therapy for localized lesions, 2 Altrogen moustard, or radioactive materials for intracavitary Infoction for malignant clluskons and ascites. BIBLIOGRAPHY 1 BALEN, WH Abnormalities in Celdun Metabolism in Malignancy Effects of Hormono Therapy Am J Med 21 714 1056 2. BATEAN J C and CARLTON HN Palliation of Vammary Carcinoma with Phosphoramide Drugs, LAM.A., 163 8 1958 3 ENDICOTT A M The Chemotherapy Program J Nat Cancer Inst. 10 275 1957 4 HUGGINS C Endocrino Methods of Treatment of Cancer of the Breist, J Nat Cancer Inst 15 I 1954 5 KENNEDY B T and NATTINSOY I T Effect of Sox sterol Hormone Therapy in Advanced Breast Cancer J AMA 152 1135 1953 6 KENNEDY BJ Fluorymesterone in the Treatment of Advancd Breast Cancer Cancer 10 813 1957 7 LEWISOV E F TRIPLC F H., and GANELIN RS Advanced Mammary Cancer Treated with Sex Hormone, JAVA 102 1429 1856 8 NATAANION IT Clinical Investigative Experience with Steroid Hormones in Breast Cancer Cancom 5 751 1952 O SHDKIN M B Luas, E L. STONE RS and BELL, H. G Cancer of the Breast Analysis of Frequency Distribution, and Vortality at the University of California Hospital 1918 to 1947 Inclusive Sung Gynec & Obst., 94 615 1952 ·126 Treatment of Metastatic Breast Cancer 13 served occasionally following the intravenous administration of nitrogen mustard Reports of benefit from the phosphoramide group of drugs have not been confirmed 2,12 At present, the most useful application of chemotherapy in the management of breast cancer is in the control of recurrent malignant pleural effusions and ascites The direct injection of nitrogen mustard into the involved cavity will eliminate or suppress an effusion in approximately two-thirds of the patients This method of control compares favorably with results obtained using radioactive gold or chromium phosphate It has the important advantage of being easily administered, readily available, inexpensive, and without radiation hazard The procedure is carried out as follows Approximately half of the pleural or ascitic fluid is withdrawn and nitrogen mustard is injected into the cavity The dose employed is 04 mgm kg of body weight, amounting to a total dose of 20 to 30 mgm in the usual patient The solution is prepared immediately before administration, so as to avoid loss of potency through hydrolysis, and is dissolved in 50 cc of normal saline In patients with pleural effusions the drug is injected through the same needle used for thoracentesis, whereas in patients with ascites it is injected at a different site in the peritoneal cavity by means of a long, #22 Care is taken so that a free flow of fluid is obtained from the cavity before the drug is injected, assuring that it is not injected into the tissues Following injection of nitrogen mustard the patient is placed in a variety of positions in order to distribute it throughout the pleural or abdominal cavity On the following day the remaining fluid is withdrawn from the body cavity Pain is seldom experienced following injection of nitrogen mustard into the pleural cavity, but pain, nausea, vomiting, and peritoneal irritation may be experienced for several days following its injection into the penitoneal cavity Nausea and vomiting usually are experienced within a few hours following administration of nitrogen mustard, but can be controlled with 25 mgm of chlorpromazine, intramuscularly, given immediately before the procedure and at two hour intervals for 2 or 3 doses following the injection Bone marrow depression is mild with this method of administration, and repeated courses necessary of nitrogen mustard are given at two or three week intervals of The hematologic status is watched carefully nonetheless Extra caution should be employed in patients who have received extensive radiation therapy to bone gauge needle metastases A suggested plan of therapy for disseminated mammary carcinoma is shown in Table 5 It is anticipated that many new and more effective synthetic androgen and estrogen derivatives will be made available in the near future In addition, a clarification of the value of presently available hormones will result from the cooperative research effort being conducted by the National Cancer Chemotherapy Service Center of the National Cancer Institute, and a large group of cooperating medical schools ·Treatment of Metastatic Breast Cancer 127 Table 5 Poumenopausal Premenopatleal of Early Monopoiual Bono Lesions Predominating 1 Androgen Soft Tluo Predominating 1 Estrogen I Castrition 2. Androgen 2. Estrogen 2 Androgen 3. Choice of a Adronal cortical steroldscupportivo b Ablative surgery-hypophysectomy, adrenalectory c Exportinental chemotherapy-akylating agents, antimetabolitos, etc. At any Hmo durtog course of disease 1 Radiation therapy for localized lesions. 2 Aſtrogen mustard, or radioacth o materials for intracavitary injection for malignant effwions and ascites BIBLIOGRAPHY 1 BAKER, WH Abnormalities in Caldum Metabolista in Mahgaancy Effects of Hormone Therapy Am J Med. 31 714 1856 2 BATERIAN J C, and Cantov HN Palliation of Mammary Carcmoma with Phosphoramide Drugs, J.AMA 162 8 1058 3 ENDICOTT K.M The Chemotherapy Program J Nat. Cancer Inst., 18 275 1957 4. HUGGINS C Endocrine Methods of Treatment of Cancer of the Breast, J Nat Cancer Inst 15 1 1954 5 KENNEDY BJ and NATHANSOV IT Effect of Sex steroid Hormone Therapy in Advanced Breast Cancer TAMA 159 1135 1953 6 KENNEDY BJ Fluotymesterone in the Treatment of Advancd Breast Cancer Cancer 10 813 1957 7 LEWION EF TAUBLE, F H., and GANELIN RS Advanced Marmar Cancer Treated with Sex Hormones, JAM.A. 182 1429 1958 8 NATHANSON LT Clinical Investigative Experience with Sterold Hormones in Breast Cancer Cancer 5754 1952. O SWOIN MB Lucia, E L. STONE RS and BELL HG Cancer of the Breast Analysis of Frequency Distribution, and Mortality at the University of California Hospital 1918 to 1847 Inclusive Surg Gynec & Obst, 94 645 1952.

·128 Treatment of Metastatic Breast Cancer 10 TREVES, N An Evaluation of Prophylactic Castration in the Treatment of Mammary Carcinoma, Cancer, 10, 393, 1957 11 Castration as a Therapeutic Measure in Cancer of the Male Breast, Cancer, 2, 191, 1949 12 ULTMAN, J E, HYMAN, GA, CRANDALL, C, NAUJOKS, H, and GCLLHORN, A Triethylenethiophosphoramide (thio-TEPA) in the Treatment of Neoplastic Disease, Cancer, 10, 902, 1957 13 WEISBERGER, A S, LEVINE, B, and STORAASLI, J P Use of Nitrogen Mustard in Treatment of Serous Effusions of Neoplastic Origin, JAMA, 159, 1704, 1955 ·pter 11 RENALECTOMY AND METASTATIC EAST CANCER E first successful total adrenalectomy in man was performed by Huggins and in 1915 on a patient suffering from carcinoma of the prostate Adrenal iclencs dc clopeel since cortisone and similarily active compounds were allable at that Umc With the advent of cortisone Huggins ngain attempted Jalectomy for the treatment of metastatic arcinoma In 1952 he published al papers on adrenalectomy describing its effect on patients with metastatic noma of the breast ** e procedure advocated by Huggins consists of oophorectomy if not already med, and total adrenalectomy The chief contmindication to adrenalec is extensive livet metastasis and probably cerebral, as well. Although 3 are varinble, approumatel one-third of the patients show some palliative it. In all of the series of any numerical size it is evident that the majonty tients arc unresponsive When effective there is decrease in pam from bony Hascs, regression of soft part recurrences, absorption of pleural and ascitic and a very definite overall mprovement in well being The duration of At varies, as a nilo pine to twelve months, but periods up to twenty four hirty months are reported 1 2,3,11 13 The rosult may be dmmatic and this is hept in mind despite the numerous failures cause of these occasionally dramatic results the criteria for selectmg patients prime importance Unfortunately no such reliable criterin have yet been coming in his initial reports, Huggins7** mpression that the histologic m of differentiation of the tumor may predict its sensitivity to adrenalectomy not been found acceptable Age is also an unpredictable factor and has n varlations young premenopausal women may do well, and older women do beneficial response whatsoever although the reverse of this would be ted Personli 17 designed a test for the selection of pationts based on mm excretion studies of the urine Erceptions to this occur and if only issue metastases are present this determmation is not applicable difications of oophorectomy and total adrenalectomy have been reported.? 45 e series, in addition to oophorectomy and ndrenalectomy the adrennl corter re-implanted into the mesentery of the small intestine In this way it is ned that adrenal cstrogens and androgens are metabolized by the liver mume manner as the gonadal steroids, by transplanting the adrenal cortex ( 121 ) 0 ·130 Adrenalectomy and Metastatic Breast Cancer into the portal circulation The liver would thus inactivate the so-called “carcinogens” without complete inactivation of essential cortical steroids. Twenty-tivo patients with adrenal cortex autotransplantation were studied and it was demonstrated that the transplanted adrenal corter was viable and functioned physiologically The therapeutic results obtained by this method closely parallel those reported by others with oophorectomy and adrenalectomy alone.2,3,6,8,11 Its advantage lies in the smaller dosages of cortisone necessary to maintain the patient postoperatively, but all require some substitution therapy Galantes has reported on a few cases in which the adrenal vein was anastomosed to the splenic vein, with similar results Because medical (cortisone) therapy is relatively satisfactory adrenal grafting procedures are not commonly performed The recent long term follow up report of Dao and Huggins evaluates 52 consecutive patients with metastatic mammary cancer who underwent adrenalectomy They felt that “significant remissions occuried in 20 patients” and 2 survived more than five years A study of their statistics reveals that 37 patients were dead within one year, 43 within two years, 45 within thiee years, and 49 within four years Although the mean survival of their patients with generalized metastasis was 27 6 months this must be evaluated in relation to the actual number surviving As with all traumatic therapeutic measures, particularly in evaluation of our present problem, 1c, adrenalectomy for cancer of the breast, it is imperative to give careful consideration to the following 1 The quality of the therapy, extensive surgery 2 The relative number of patients that may be benefited 3 The quality and duration of the therapeutic result, noncurative The surgery is extensive and need not be emphasized (see below) Comment has already been made regarding the number of patients benefited It is felt that the quality of the therapeutic result has been misleading in most reports, that palliation is more apparent than real, and not different or supenor to that obtained by the more simple measures of oophorectomy and hormone manipulation (sce P 122) One must bear in mind that the adrenalectomized patient, even with the best of steroidal substitution, is in no way a complete human being a good homeostasis The adrenal glands secrete numerous steroids, few of wluich are replaced, and these are modified synthetic products They are given at intervals which may bear little relationship to the physiological needs of the patient. Certamly such patients are able to funchon, but their resistance is low, not only to infection, but to the stress and strain of ordinary environmental influences !" On the other hand, adrenalectomy has reinforced our belief that certain mammay cancers demonstrate partial hormone dependency When the effect of oophorectomy and oral or parenteral hormoncs has subsided, it is a procedure 11 orthy of consideration This may be especially so in patients who have responded well to previous hormone therapy To cmploy this procedure earlier ·Adrenalcctomy and Metastatic Bread Conco 131 in the course of the disease does not seem warranted in view of the sometimes dramatic results of oophorectomy and hormone treatment alone Perhaps the greatest contribution of adrenalectomy is that it has emphasized the inter relationship of certai cancers and the endocrine system The Increased knowledge in physiology and chemistry derived from studies of the adrenalec tomized patient will prove valuable in reachmg a physiologic solution to breast Cancer Pre- and Postoperative Management In addition to a thorough physical examination, and frank discussion with the patient and her family of the operation and its results the following studies are obtained before adrenalectomy is performed 1 Y mys of chest and sheleton 2 Electrocardiogram 3 Non protein nitrogen 4 Serum Sodium 5 Serum Potassium 6 Serun Chloride 7 Serum Calcium 8 Scrum Phosphorus 9 Serum Protein 10 Packed cell volume 11 Complete blood count 12 Urne analysis Experience has shown that no special preoperativo medication is necessary? steroid administration is started when the patient is on the operating tablo А cut-dowo" using a #13 or #15 gauge polyethylene tube is placed in an arm or leg vein and 1 liter of 5 per cent glucose in water containing 100 mgm of hydrocortisone, is administered by constant drip (Plate 42) Dunog induction of anesthesia 250 cc are mjected rapidly and thereafter blood pressure is kept at the patients normal preoperative lovol by varying the number of drops per minute By the end of the operation 400 to 600 cc containing 40 to 60 mgin af hydrocortisone have been given Whole blood is added as needed either through the same tubing or through another "cut-down" During the first trventy four hours about 100 to 200 mgm of hydrocortisone is given Intravenous hydrocortisone solution is continued until the patient is able to take oral medica Hon without pausca or vomiting, usually by the fourth or fifth day alternative cortisone m dosages of 100 to 150 mgm a day may be given intra muscularly should the intravenous route be troublesome Because of the short life of hydrocortisone about four hours, care is necessary lest the intravenous apparatus shut down and the patient be without medication By using cortisone intramuscularly this danger is avoided In some patients who are very debilitated or aged 25 to 100 mgm of cortisone are given fatramuscularly the night before surgery Five to 10 mgm of desory corticosterone (DOCA) sublingually and oral salt, 4 gm, can also be given the day before : This has not been necessary in the majority of patients' As en ·132 Adrenalectomy and Metastatic Breast Cancer mgm of The total daily postoperative fluid intake is kept at about 2500 cc, of which 1000 to 1500 cc is normal saline By the second day only 75 to 100 hydrocortisone are needed There is a gradual leveling off to between 50 and 75 mgm daily When oral hydrocortisone is given, 40 to 60 mgm a day aic often sufficient, and at the time of discharge 20 to 40 mgm a day are satisfactory Theic are periods when the requirements increase due to a variety of clinical conditions 13 On the third day an ampule containing KCI 1.8 gm, MgCl, 0.5 gm, and CaCl, 06 gm is given and continued daily to prevent hypokalemia Serum potassium and sodium levels are checked at frequent intervals Sodium chloride in entenc coated tablets is given in doses of 1 gm 3 times daily after the tenth day In some patients a persistently low sei um sodium level is restored to normal by an injection of 15 to 25 mgm of the long acting, repository form of DOCA, desolycorticosterone trimethylacetate, once a month Ini others, 2 mgm, sublingually, daily, of regulai DOCA as maintenance dosage is used If shock occurs during the operation or afterwards it is combated with a 16 mg./Liter solution of L-Arterenol (levophed), 50 to 70 drops per minute, oi regulated as needed to maintain normal blood pressure (Plate 42A) Renal shut down and paralytıc ileus are other complications which are dealt with as thev Close postoperative supervision, especially of the pulse and blood pressure, are essential, in addition to strict attention to fluid balance and clectrolytes. alise Surgical Technique of Adrenalectomy Removal of the adrenal glands is combined with bilateral oophorectomy of the latter has not been previously performed The abdommal approach through a long upper transverse incision is strongly recommended by some Il enables one to remove the ovaries simultaneously and is essential if cortical transplant is to be done A posterior approach, through the back, is also adequate, and by using two teams of surgeons probably quicker The adrenal glands arc, after all, subdiaphragmatic organs and more often than not situated high m the retroperitoneal space 10 They are more superficial when approached from behind than up front Nagamatsu!" has described a dorsolumbai mcision which facilitates removal If this method is used, the ovaries are removed first hy laparotomy The patient is then turned, and adrenalectomy performed Lessened morbidity, dımınıshed leus, simultaneous exposure of each adrenal (if two teams operate), and shortened operating tinc arc the advantages of this approach. There is some disadvantage in turnmg the patient after laparotomy, wud citra caution is necessary in turning the patient buch again follow my drenale. Change in position may caused marked depression of the blood pressure Iside from these two factors the method has proved useful and satisfactori Since ton

·Adrenalectomy and Metastatic Breast Cancer 133
PLATE
42
5% glucose
Blood
1% salino
100 mg
Lovophod
16 mg / litor
Hydrocortone
alcohol
in ! liter
5% glucose
in water
A
INCISION
0
А
cut down
to arm
POSITION
Cut down
to leg

·134 Adrenalectomy and Metastatic Breast Cancer the abdominal route is more familiai, the posterioi approach only is illustrated m accompanying diagrams The patient is placed prone on the operating table with the kidney sest lymy just below the costal margın Slight “jack-knife” position is used (Plate 42) Endotracheal anesthesia is essential Incisions are made in curved, hockey stich fashion, starting at the ninth doi sal spme and carried downward and laterally along the course of the 11th and twelfth ribs to the maigin of the nectus muscle (Plate 42) Overlying musculature is incised and short segments of the cleventh and twelfth ribs are resected medial to their angles (Plate 43). The entue ubs are resected in the diagram, but this is not necessary. The costovertebral ligament is sectioned exposing the diaphragm The lateral arcuate ligament of the diaphragm (Plate 43) is divided below the pleural reflection, although in many mstances the pleural cavity is entered The retroperitoneal space with kidney and adrenal glands is exposed (Plate 43) The adrenal glands are removed (Plates 44, 45, 46), usually with a little more difficulty on the right side due to the provimity of the vena cava The wound is sutured in layers (Plate 47) The pleural cavity, if entered, is closed under positive pressure with full lung expansion No drains are used (Plate 47) The patient is cautiously turned supine, and placed in bed.

·Adrenalcctomy and Metadatic Breast Cancer 130
PLATE 43
Adrenal g
Lotissimus dorsi m,: Serratus posterior m
Hith rib
Lung
12th
rib
Perirenal fat
Diaphragm and
costovertebral membrane
PLATE 44
Left adrenal
gland
WA
But

·136 Adrenalectomy and Metastatic Breast Cancer PLATE 45 Right adrenal gland --Liver Suprarenal V. ligated Inf. vena cava Renal v. facile PLATE 46 L. Dissector Right adrenal gland Liver.. Suprarenal Vs ligated Inf vena cava: M. Greennend Renal V-

·Adrenalectomy and Metastatic Breast Cancer 137
PLATE 47
4. Good
Suturing diaphragm and costovertebral membrane

·138 Adrenalectomy and Metastatic Breast Cancer BIBLIOGRAPHY 1 BERNSTEIX, DE, BISKIND, GR, and Brown, A L Autotransplantation of the Adrenal Cortex to the Mesentery Combined with Adrenalectomy and Oophorectomy in the Treatment of Metastatic Carcinoma of the Brcast, Am I Surg, 92, 174, 1956 2 CADE, S Adrenalectomy for Breast Cancer, Brit Med J, 1, 1, 1955 3. Dao, T L., and HUGGINS, C. Metastatic Cancer of the Brcasl Trented by Adrenalectomy, JAMA, 165, 1793 1957 4 EISCMAX, B, HUGHES, R, SUMATERS, W, and Taylor, F Human Acirena Corlical Autograft into the Portal Circulation, Ann Surg, 142, 961 1955 5 GALANTE, M et al Bilateral Adrenalectomy for Advanced Carcmom.t of Breast with Preliminary Observations on Effect of Liver on Metabolism of Adrenal Cortical Steroids, Ann Surg , 140, 502, 1951 6 GALANTL, M, FOURMICR, DJ, Wooj), D A Adrenalectomy for Metastatic Breast Carcinoma, JAMA, 163, 101], 1957 7 HUGGINS, C, and Scott, W W Bilateral Adrenalectomy in Prostatic Cancer Clinical Features and Urmary Excretion of 17-ketosteroids and Estrogen, Ann Surg , 122, 1031, 1945 8 HUGGINS, C, and BERCE\STAL, D MI Inhibition of Human Mammary and Prostatic Cancers by Adrenalectomy, Cancer Res, 12, 134, 1952 9 Huggins, C, and Dao, T Adrenalectomy for Maimary Cancer Ann Surg 136, 595, 1932 10 NAGAMATSU, G R, LLRMAX, P H , and BLIVI, VII The Dorsolunbar llap Incision, J Urol , 67, 787, 1952 il PEARSOY, OH, WEST, CD, and HOLLANDER, V P Evaluation of Endocrine Therapy for Advanced Breast Cancer, J A VA, 154, 234, 1951 12 Pearsov, OH, Vin, C Li, MACLEIN, T P and Lipsin, MB Vanagement of lietastatic Vammary Cancer, J AMA, 159, 1701, 1955 13 SIMKIX, Bexy Long Term Management of Patients After Adrenalectomy, California Ved , 87, 383, 1957 ·Chapter 12 HYPOPHYSECTOMY AND METASTATIC BREAST CANCER Tire anterior pituitary gland produces stictal hormones which may influenco the growth of breast mincer These are follicle stimulating hormone and interstitial cell stunulating honnonc which control ovarinn steroidogenesis Jactogenic hormono which luas a direct cffect on breast tissue is well as maintenance of ovanan steroidogenesis adrenocorticotrophic hormono which controls adrena steroidogenesis and somatotrophın, or growth hormone which may directly stimulate the growth of cancer tissuc Thus hypophysectomy might be expected to modify the hormonal environment of mctastatic breast cancer by climinating these hormones Many methods for the destniction of the human pituitary gland are currently being studied These include Surgical hypoplysectomy by the trans-canın, trans septal-sphenoldal, trans-cthmoid sphenoidal or the tmns antral sphenoldal approaches irradiation hypophysectomy by proton bombardment with the syn chrocyclotron or by intmpituitary Injection of radioactive substances such as radon seeds, yttrium 90 pellets or phosphorus 32 ns colloidal chromic phosphate or pituitary stalk section which accomplishes a functional hypophysectomy by separating the anterior pitutary gland from the hypothalamic control centers There Is no agreement regarding the superiority of methods which attempt actual removal over methods attempting destruction or neutralization As a matter of fact there is some question as to whether total removal is essentul for effective therapy against mammary carcinoma 2.45 70 10 That method which permits effective removal of function with the least danger and the fesyest complications is the most desimble These critcrla are satisfied with direct vision of the deld including the important strictures which are in anatomical relationship to the sella This consideration empluasizes a major advantage of the methods requiring craniotomy Extirpation of a normal pituitary gland by transfrontal craniotomy allows tho greatest control in protection of the hypothalamic and optic apparatuses, and marimum opportunity to prevent or control bleeding from the numerous arterinl arul venou structures in the mmediate neighborhood Experlence shows, hou ever that complete removal has been very infrequent ** The trans septal sphenoid approach to the pituitary gland was developed by It has been used extensively in the treatment of pituitary Oscar Hirsch' in 1910 ( 130 ) ·140 Hypophysectomy and Metastatic Breast Cancer tumors 1, For a subtotal, functional hypophy sectomy it is a logical approachi. although by craniotomy or by a trans-antral-sphenoid technique, wider surgical cyposure is obtained, and a more complete lypophysectomy accomplished It is a non-shocking procedure, accompanied by little blood loss and performed under local anesthesia If complete hypophysectomy is shown to give better palliation, more extensive procedures are warranted. HORMONAL MANAGEMENT OF THE PATIENT UNDERGOING SURGICAL HYPOPHYSECTOMY Preoperative determinations of the following afford a baseline for postoperative comparison serum sodium, potassium, lica, protein bound 10cme, and me pituitary gonadotroplin titer The plan of hormonal management is as follows Cortisone acetate, 100 mgm , intramuscularly, the night before and the morning of surgery Hydrocortisone alcohol, 100 mgm, in 500 m) 5 per cent glucose in water, intravenously, slowly during sugery Cortisone acetate, 50 mgm , intramuscularly, every sı hours postoperatively This dosage is slowly reduced and gradually shifted to oral cortisone so that by the fifth postoperative day the patient is on a daily oral maintenance dose of 25 to 50 mgm, of cortisone Fluids 2500 ml daily, including 5 to 10 grams of NaCl (86 10 172 mEq Na daily) Urine output is carefully measured, and if urine flow is consistently greater than 300 ml per two-hour period, 3 units of pitressin tannate in oil is given intramuscularly and repeated every two or three days as indicated Vital signs are followed carefully during the immediate postoperative purwod Should hypotension oi shock develop, in addition to usual surgical management. 100 to 200 mgm of hydrocortisone hemisuccinate as administered intrattenonly This complication rarelv occurs Diabetes insipidus occurs more often following mlracramal procedures in which the pitutary stalk is traumatized It may be a tansient or permanent development after hypophissectomy by my route and responds to pitressi tannate in oil, 3 units intramuscularlı ciery two to three class Serum electrolytes are followed postoperatı cly to be certain that corticou replacement is adequate Thyroid cxtract is not routinely ynen breuise the desclopment of hypothyroidism four to sn wechs postoperatively max bunului 110es to the completeness of hypophysccomy Anothier udos to the compleiros Thess of lipophysectomy is the disappearance of anterior potentiri goli kloroplan from the urine Il is divisable, therefore, to caterinine the vetme protein bunti I luật and the urme vonadotropiun liter ad monthly introds after bispo plos sectors ·141 llypophysectomy and Aletastatic Breast Cancer Totally hypophysectomized patients are usually well maintained on 25 to 50 mgm of cortisono (or 20 to 40 mgm of hydrocortisone) orlly in divided doses daily and I thyroxine 0.2 mgm in a single oral dose daily During periods of stress the dose of cortisone is increase If severe it is wise to revert to parenteral therapy with intramuscular cortisono nectato and intravenous hydrocortisone hemisuccinate administering a total of 300 to 100 mgm of steroid over a twenty four hour period DISCUSSION Hypophysectomy by whaten er route pxrformed is n palliative procedure of limited value. It is the final method of treatment which one may employ for a patient withi disseminnted breast cancer It lins not supplanted adrenalectomy though theoreticalls it could In a few instances acrcnnlectomized patients Will show further regression of their metastases following hypophysectomy ** 10 Unfortunately by the time most patients stop rcsponding to the effects of adrenal cctomy they are too near denth to warrant furtlicr opentive procedures In addition, results with oophorectomy and hormones, though far from satisfactory are yet good enough not to be supersedled by hypophvsectony (or ndrenalectomy) performed in nn earlier stage of the patients diseaso Whether performing hypophysectomy at an earlict stage in the course of progressive metastases would increase comfortable longevity is open to question and awnits further study By the relatively simple means of oophorectomy and hormone manipula tfor one appears to accomplish equal results It is only after the effect of hor mones subsides that the operative proceduures of adrenulectomy and ultimately hypophysectomy are considered The reported results of surgical hypophysectomy in patients with metastatic cancer of the breast indicate that about 20 to 50 per cent will achieve some pallia tion of their discase 2:710 This is of short dumtion, three to six months It is associated with objective regression of metastatic lesions particularly in the lungs or slcleton Subjective improvement, especially relief of pain, may be marhed Older patients and patients with liver or brain metustases are less likely to respond Patients who have had some prior response to custmtion or hormone therapy do better Experience with trans septul sphenoid hypophysectomy has not been dramatic yet this appronch is simple, carries littlo morbidity and is worthy of trial if hypophysectomy is to be performed BIBLIOGRAPHY 1 EDELSTI GA, CLEADHILL CA Lioy AR RODGERS HH TAYLOR, A R., and WCLBOURN RB Hypophysectom; Combined with Intrasellar Irradla with Yttrium-00 Lancet 1 462, 1958 9 ESCHEN, R Roti F and COTTIR, H Parunasal Transethmoido-Spheroldal Hypophysectomy in cases of Vletastasizing Breast Cancer Ann. Otol. Rhin & Laryng 66 1009 1957 ·112 Hypophysectomy and Metastatic Breast Cancer 3 Escuer, F. Roth, F, and COTTIER, H Die Paranasale Trans-ethmoido-splievodil Hypophysektomie beim Vetastastieren Mammakarzinom. Schuciz Hed Wchnschir, 88, 19, 1958. 4. FLRGUSSON, ) D Implantation of Radioactive Material into the Pilmari fur Control of Prostatic Carcinoma, Brit ). Urol 39, 215, 1957 5 HECK, WE, MCNAUGHT RC, GREENSPAFS, and K PLAY, HS Trains Septal-Sphenoid Pituitary Surger, Laryngoscope, 67, 906, 1957 6 HIRSCH, Oscar Symptoms and Treatment of Pitutarı Tumors A Morte archi Otolaryng, 55, 268, 1952 7 KEVXCD), BJ, FRENCII, LA, and Pritov, W T Hypophysectomia Advanced Breast Cancer, New England ] Vled , 255, 1163, 1950 8 Lurt, R, and OLIVECROVA, H Hypophyscctomy in the Management of Veoplastic Disease, Bull New York Acad Med, 33, 5, 1957 9 PCARSOY, OLAF Hypophysectomij, Springfield, Ill, Charles C Thomas, 1957 10 Proc Royal Soc Med , 50, 859, 1957 Discussion of Hypophysectomy for Cancer 11 Topias, CA, LAWRCACE, H, Bonn, ) L, McCovs, RK, RobiT.) E. ANGER, H 0, Low-Beck, B Vd, and HuggiS, CB Pitunturi Irridtion with High Energy Proton Beams, Cancer Res, 18, 121, 1958 ·INDEX Principal reference inxllcatel In italic type А Biologie cmsiderations of radiotherapy 103 preletemminism 58 Bopy of borcast Jump 11 62 of lymplı noles, 02, 03 89 83 Sco Opera tion choice of Surgical tedintqs Blveling from the nipple 33 Blood loss 78 Biurc comel cyst Sce Cysts Bone metastaser treatment of 118 Breast Sec Benign. Cancer Button like tunsor 47 с ANORTHOX 60 Abscesses, 53 Iccessory mamman tsue 46 Adal FE 50 Adenocystic disease 10 Adenofibromas Sec Filmadenomus Adenost, 19 Adquocthc procedure 80 Adrenal glands 58 132 stokk, 125 treatment with, 125 transplant, 130 Aurenulectunny 85 192, 129 management of 131 results of 130 technique of 132 Androgenik hormones, 123 therapy with 124 e of 123 Age Eod Cance 59 OL Sec Diese citity Ambulation, 79 Anatomically therapeutic, 11 Anatomy Sec Surgical teclinkmes. Androgeos, 27 Acesthesla, 21 Anomalies. See Classification of tumors Antibiotics, 53 70 Aodety concerning I eart tumors, 18 Apocride glans, 18 Arrolar See Papillomes w Tarcolar Aptration of cysts, 20 Seo Lysts. Atilla, led of metastases, '88 See Lymph nodes. CALCLAIT L, hypercalcenila, 124 Calctum cictction tcst, 129 Cance and bleeding from nipple, 33 anal mastitk, 30 in thc nuk 47 85 of breust 7 13 58 of prostate 47 85 simultaneouis, 83 Carcinoma in mu 14 inflammatory 16 Ser Cancer Core, pre-operativo Sec Adrenalectomy lly pophysectomy Castration lry radiotherapy 118 123 Sce Adjunctive procedures Dophorectomy Orchfectomy Chemotherapy 192. 125 Chronic cyntic mastit, 19 and cancer 30 Classifiation of breust tumors 1? Compliations, 7 78 Contraindications. Sec Disease entity Opcta bility Cortisone. Sco Adrenal. Hypophysectomy Caterie, Viell hitet, 114 to detcrinide ancer 14 30 to determine mastitis, 14, 30 Cytologic amcars, 19 ( 113 ) B BLANCN parenchymatou hyperplasi, 19 tumori. of breast, 18 Bilitetul breast cancts, 83 ·144 Indea Cistosarcoma Philodes, 42 Cysts, aspiration of, 20 blue come, 14 of breast, 19, 20 D GA۱۱ ۱۲،۱۰ 1(); Guant fibroadenomy kom i Src Cistos Gold, radioactive, 117 Grading of tumors 155, 88 See Il tolon Granular cell mvoblastom., 13 Gross appearance of tumors. 13 11 15 16 17 Ginecologic disorder 19, 11 Gynecomastia, 16 17 II DANGER of breast lump, 18 Dulay, 89 Derivatitis sadiation type, 79 Diabetes insipidus, 140 Diagnosis of breast tumors, 7, 11, 18, 58, 59 Scc Disease entity Transillumination Dimpling of shin, 20 Discharge from nipple Sec Blecdmg Dissection of internal mammary nodes, 63 Sec Biopsy Lymph nodes Surgical techninies DOCA, 131 Drains Scc Surgical techniques Dressings, 78 82 Drugs Sec Hormones Nitrogen mustarul Phosphor.imde HAACLASI, CD, 60, 62 109 Halstei, Il S. 58. 61, 106 llemorrhage post-operative, 78 Ileredity and cancer, 59 Ilitologs and rachotherapy, 105 100 and results, 88 Holghin's disease, radiotherapy of 116 Hormone dependence, 7, 27 17 Ilormone multion, 27 Treatment, 122 of breast Cancer 81 123 of chrome (14116 m.tits 19 of gynecomastial, 18 Suc dream lealom Ilipoplasectomy Huggins, C, 129 Ily dated lumor of lorearst hu listrogens Ilypertrophy of breast fissure, 11 Ilypophysectomy 83, 122 139 management of patient, 140 results of u Su Surgical temps Ily poplossa Set Ilypoplussectomy C Fran VOSS und fal necrosis, 16 Edlema Scc Lumplieduma Fiducation of July, 11, 59 Eflusions, pleural 126 treatment of, 126 Electrolytes Suc Adrenalcctomy Typophav. Sectomy Endocrine balance in minecomastia 17 Crysipelord S1 listrogi 13- androgen pattern, 27 Estroven stimulalom 27 Estrogons, 27, 121 Iruperestrovcism, 27 Irtment with 121, 125 Litended radical misteccoms, 91 Sur Surtial finansies INCIDINT of humun tumors, 19 of cancer 18 for Cancer Incestions Sue Surgic il tampoe Inflammation Sir Abasses Inflammatori (remom. 16,00 Inoperable (almeer of Israel, and reluthur dp 115 Su Operability Intimnul mimmin lympha mmes for 110plı 110les Mechaseinum Interse epulothoracic impril 2016 lontution 102, 101 Isoclos (ursas 103 112 111 Isotopen the folpi ulit line of 117 F 111 ( SOSIY 13 10 To ror of lyrcin (me er 11 16 15 ۱۱۱۱۱۱۱ | (rtرار ل milion ITC On. 13 11 Turori 16 mislitin, 30 I bruses of borr 157 tissant pulum in 79 Iuftestations of rollenti Ironlar tomoni1011 13 26 Topi 1 11111!!! VOL llisoplell 11.. Liftition in the ·Inder 145 Votion of ann 78, 9 \uscle trumplant of Litl»lmus 82 Lactation and cutourcoin 43 and treatinxent, 80 Sec l'rgiliny Lhomas 16 Lher role in mastitis, 97 Location of cancer 69 01 05 98 100 Ser Lymph wxles Site Lymph nodes axillan, 15 61 100 efect of fm oli ennent 89 In chronte inustius 20 huternal miminary 10, 01 M 9103 108 prarasternal, 83 spradavicular 61 91 106 107 Sre Blops Lytophanglosarcona 78, 82 Lyinphatic drainage of barist 91 01 106 Ljiapbedkuul of am, 78 79 81 Scc Swelling Lmp la lucast 11 18 Wirri Sre lapillomas of duct Vitrol, en mustarel, 128 Tursing and cancer 50 83 Soo Lactation Pregnancy Nutritional deficiency 26 of an OOPIKROTOTY 81 80 85 110 129 129 132, 141 und rullollerapy 116 Operability 59 Opxtation, choice of 62 Sec Sugical teel niques Opposite lucast 59 82, 83 Orthkectomy 81 85 123 Ongel anal radiation 101 P VALE breast cancti 85 Valmutition in gynecomastia 48 Mammography See Roentgenography Varriage and breast cancer 59 82 Sec I'ret nancy Vanried Bath Anu Cncu 59 Vasectomy anxl cystowrconin 11 Sce Radi cal mastectoniy Simple mastectomy Surg! cal technkjes Vartodynia, 19 (27oplasia, 10 IcWhirter H., 79 113 Valbastioni dissection, 90 100 results of 00 Sec Udaan. Illangenstern mediotherapy 110 Vediamaton. Sec Lymph nolex Jlalkal treatuxont of gynecomastia, 28 18 of mastita, 27 Sce Hotmatic treatment of cancer Mcdicolegal. Sec Tmuma Alepopausal patient 81 122 lenses relation to breast tunnor 19 to mastith, 97 39 Vietastaser, 81 BI 106 122 touto of 15 to endocrine plands 16 ratmeat of with adrenales torny 129 with hoTiOTOS. 122, 126 with hypophryxectony 139 with radhith Tapy 116 Sec Lymph Doiles Alege Willy 62 Alines and radiotherapy 103 Solici masectomy 65 10 li shektal 61 I allation 81 with liomuones, 122 with radiotherainy 110 Sec Adrenale tony Hypophysectomy Papillon lepliantiasis, 44 tunars, 14 Pupilloming of the duct 14 33 Pipillomatosis Sco Papilloma l'arutemal radiotlıtepy 110 lathology of breast tumor 12 Mosphoranklo drugs 120 Plxophorus, 130 Physical considerations of motitap, 102 Physiologically therapontic, 11 Physiology of breast cancer 7 Pitaltary gland 58. Sec Jlypoplysectomy Pleural clusions 128 I ortal correlation and actual transplant 130 Position on operating tahlc 21 lost operativo caro 78 82, 08 131 ndlation, 109 Precancerous condition 31 Becletcriinisoy, hlologic 5.5 Pregnancy and ancer 50 60 82 and cystosarcom, 43 and fibroadenomas 41 and treatment, 60 Sco Optibility Inc-operativo cure Sed Adrenalectomy lly pophysectomy ·116 Inder S Pre-operative radiotherapy, 108 See Raclia (10n Primary radiotherapy, 111 Inminste Sec Location Prophylactic mastectomy, S1 Scc Opposite Dorcast Proslati Cancer, 47 85 Prosthesis, 79 Psychology of breast Pumps, 11, 18, 79, 122 Q QUADRANTS of brcast, 61 Scc Location Lymph nodes Lymphatics Site R Ran), 102 Radiation therapy, 7, 102 and castration, 118 and pallation, 116 at Stanford University Hospital Sce Mediastinal effect of, 105 SARCOMAS or breast 1217, 116 and fibroadenom.is, See Cistosoomus Sarcomatous change: 11 Slucer celge. 19 Schimmelbuschis discale, 19 Sclerosing adenomatosis 1,3 Simple mastectomy 63, 64 63, 71) SI Smultaneous breast Cancer, si Sinuses, draining of, 53 Sitc, 107, 89 Sce Location Swc of cancer SS, 107 Special factors and results, SS Splenoid Scc Hypophyscclom "rans- Spread of cancer, Bi 106 Su Limph nodes Vetastases Statistics and breast cancer, 56 concerning mastitis and cancer, 19, 21, .30) 31 Steroids Sue Adrenal lly pophusis Subarcolar, 01 sue l'apllomas Suction catheters 79, 82 Sukowitch test 121 Supervoltage 102 Surgical techumelles, 7 of adrenalcctomy, 132 of craining sinuise 33 of duct papillomas 37 of cicisional biopsi, 21 of milended radical maslacom, 90 of ginecomastia IS of his popis sectomy 139 of modified maslacioni 63 of radio. 1.stuctom, 05 of simple mesteciomy. 05 Surullal rules, 20) an untreated circa 10 injury 103 of bone metastases, 11S of inoperable cancer 115 of sarcomas, 1166 post-operative, 109 pre-operative, 108 primny, 111 Radical mastectomy, 58, 65, 90, 91, 106 (Atended radical mastectomy, 91, 91 modihed, 65 simple 65 Scc Mastectomy Surgical techniques Radiosensitive, 114 Ruchotherapy, 102 Soc Racliation therapa lrat therapy Hiconds, 139 Ronction of shin to radiotherapı, 101 111 with supcriollage 111 Recurrines, treatment of So 81, with radiotherapy, 117 Results SG of rosilectors, 130 of the radial lomy, 100) of His poplenectom. of primins radiotherap, !!! of ricotheripy s5 l su Disse 102 Rer 1114 nople of ducks 31 1 11 HIVIQUES Sa Surgul tachimene Tostarski roni, 27 Sur Indromim Jonsonant Bests See Calcuni Sulhew itali Ilic rupi or breast cancer, ñ sec Dimin lily Richestion Surgu il consente trat Ulosottost. 33 'Irunnllumination, Iris-ne pril-sphetime ppi) to posluiting 139 Irunni 105 ۱۱۱۹)، 11 ، اور of surven 110 mnene a lot ga sestro!!!!!!!!! of Institis Thurspa Ilusammense te fr sit ·Inder 147 Tumar board, 7 Toons of breast. See Beniga Clissification Disease cotit Papillon WANGIASI, 0, 90 95 Wound drainage, 78 Sec Surgical techniques. U L TREATED CUT 90 Urban, Jerome 63, 91 95 MAY castration, 118 119 at Stanford University Ilospital, 80 110 tlocrap post-operatic 78 102 See Radiatlon Radiotherapy \-maiz, 102 1 Vitamin B comple, 28 Vtarotos In mastitis, 27 28 YTTRNAL 130

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