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The primary treatment of breast carcinoma
American Journal of
Obstetrics and Gynecology ~dwne
126
number
CLINICAL
O~~I~~B~~:~
4
1.;.
I Slit5
OfWW3N
This section reports opinion on the handling of clinical situations, i.e., the clinica diagnosis and management of certain disease entities. Papers should range from eight to twenty typed pages, including illustrations, tables, and figures which clarif? the author’s management. References are limited to six citations. Mail to Frederick P. Zuspan, M.D., Editor.
The primary treatment of breast carcinoma STU.4RT
M.
POTICHz4,
M.D.
T/w major ~o~il~~tions in the surgical management of carcinoma of the breast hazv been re&wed. D&its in our current kndedge halIe been pointed out in an efjort to sepawte j&t jrom theory and so hdp the surgeon in choosing the best operation for ~1,&dent with breast ~ncer, THE PRIMARY treatment of breast carcinoma continues to be the subject of debate and controversy. Recent articles in both the medical and lay press have shaken traditional concepts, making it difficult for physicians to determine the proper treatment for a carcinoma of the breast. This indecision among physicians is further reflected in the growing number of patients who are reluctant to accept radical therapy. In this maze of conflicting views, how does the clinician reach a justifiable conclusion? The medical literature abounds with studies on the management of breast carcinoma and each method of therapy is supported by survival statistics. Although the strong advocate of a particular type of surgery can point out slight differences in both the 5 and 10 year survival rates by carefully selecting certain papers from the literature, the evidence so obtained cannot justifiably be used to prove the value of one procedure over another. A better understanding of the dilemma which faces (he surgeon may be obtained by reviewing the major contributions in the treatment of carcinoma of the
breast. In analyzing each procedure and the scientific evidence which supports it, the clinician begins to recognize what facts are known and what important questions remained unanswered. With this information, he may then plan a logical course of action in treating a patient with primary carcinoma of the breast. In 1890, William Stewart Halsted,’ reporting in the Bulletin of the, ,Johns Hopkins Ho,@tnl, described an operation for the treatment of carcinoma of I he breast which consisted of removing the entire breast. a liberal quantity of skin, all of the subcutaneous fat immediately overlying the breast tissue, the pet torahs major muscle (in later descriptions, the pectoralis minor muscle was also included), and all of the axillar! fat and lymphatics. The justification for such an extensive operation can be better appreciated when one considers Halsted’s concepts of the pathophysiology of metastasis from breast carcinoma. Halsted belielred that metastases from carcinoma of the breast lvere rarely disseminated through the venous system. He referred to Handley’s’ theory of centrifugal lymphatic spread in stating, “cancer of the breast preserves in lhc main continuity with the original growth and before in\,olving 411
the viscera may become widely diffused along surface planes.” Hatsted’s radical operation was based on tht premise that cure of even ad~.anwd carcinoma of the breast could be achieved by rcmova~ of’ the breast and aN of its contiguous tymphatics. He’ further postulated, ., so it is couceivabkz that ultimately. when out. knowledge of the tymphatics transversed in cases of’ femur involvement become sufficientty exact, amputation at the hip joint may seem incticated.” In 1907, Hatsted” reported the results of his operation. ‘Ilie cure rdte with negative axittary nodes was 70 per cent and his over-all GUI-c rate \vas 53.6 per cent of 2 10 cases. This operation became the unquestioned standard treatment for carcinoma of the breast for the next 50 years. Although some surgeons have argued that Hatsted’s reputation made others reluctant to question his operation, such criticism is unjustified. Undoubtedly, the first and most important reason for the success of this procedure was that Hatsted was able to cure 50 pw cent of women with carcinoma of the breast, whereas prior to his operation wry few had been cured. Halsted stated that, “. in this country at least a number of the leading surgeons of the generation prior to mine made the pronouncement that they had not in their lifetime cured a single case of breast cancer,” Second, radical mastectomy was associated with remarkably reproducible results. It was not an operation which could be successfully performed only at the .Johns Hopkins Hospital. other surgeons using this technique in centers throughout the worM soon rcported similar results. Third, the operation was safe. IHatsted’s hospital mortality rate was on])- I .7 per cent. In the 1940’s, several investigators began to question whether a radical mastectomy was the best operation for all women with carcinoma of the breast. This chattenge to such a traditional concept proceeded atong severat tines. Many surgeons concentrated their investigative efforts on refining the criteria for operability so as not to subject incurable women to extensive surgery. The most notabte studies in this regard are those of Haagensen and Stout.’ Beginning in 1943’ and culminating in 1959’ with a triple biopsy, Haagensen and his co-authors accurately defined operability in breast carcinoma. This screening technique included apical axiltary nodes and the internal mammary nodes in the first and second interspaces in addition to biopsy of the primary tumor. In this series of highly se&ted women treated by radical mastectomy, the 5 year survival rate was 85 per cent.’ As a corollary to this work. Haagensen and Cootey”
also described precise chnicat criteria for classil’\ illg carcinoma of the breast. ,4n accurate rncans of desc rilling breast tumors is essential to the surgicat management of this disease. Certaintv, if a surgeon is to gait) any knowledge from the reports of’ others? hc nlust know the precise nature of the tumors they are operaing upon. ‘rhe Columbia Classification described h\ Haagensen is one of’ the most popular systems currently used to ctassifv breast carcinomas: others include the .4merican system, the International system, and the Manchester system. White the differences in thehe classification systems are determined bv size of’ the primary tumor or the axillary metastasis, the major features are similar. Stage .4, or Stage I, consisw of carcinoma confined to the breast atone without anv ot the grave signs of extensive mahgnanc?. Stage B, OI Stage 2, wnsists of a similar primary tumor 11ith patpabte axittary lymph nodes. Stage C. or Stage 3. consists of a tumor which has one or more of the graw carcinoma, IMtlld~~ prognostic signs of advanced edema involving nlore than one third of the breast. fixation of the primary tumor to thy chest wall, ax&w!. lymph nodes greater than 2.5 cm. in diameter, or axillary lymph nodes hxed in the axitta. Suage 11, 01 Stage 4, consists of patients rvitti distant metastasis, A second group of investigators began to cxptore the advisability of extending the operation to include tymphatics ilot cnwmpassed in the standard radical mastectomy. ‘4tthough 1 19 of the 232 patients in Hatsted’s original series underwent a neck dissection, this part of’ the operation NX eventuath discontinued. Renewed interest in extended operations, M hich inch&d reseetion of the supractavicu~ar lymph Ilodes and resection of the internal mammary hmph nodes with or without resection of part of the chest wall, was stimulated by the work of Wagensteen,7 Kaae and Johansen,’ Dah~Iversen and Tofiassen,’ and Urban.“’ In general, these operations \\ere accompanied hy an increase in morbidity and mortality rates while not improving the survival rate to any appreciabIe degree. For the most part. these operations have again been abandoned. Some investigators still feet that the Urban operation, which removes the internal mammar? lymph nodes, is indicated in patients wilh centrali? located carcinomas or carcinomas arising in lhe inner quadrants of the breast. They reason that the increased morbidity is justified in these patients because of the high incidence of internal mammary node metastasis found with these lesions. Simuttaneously. other investigators began to examine the advisability of performing less extensive operations for the treatment of primar? carcinoma of the breast. These tess radical procedures included
Primary treatment of breast carcinoma
mod&d radical mastectomy< simple mastectomy, and subtotal mastectomy (lumpect~)my) with or without irradiation. In 1948* Patey and Dyson” described an operation which differed from the smndarcl radical mastectomy in that the pectoralis m+r muscle was not removed. ‘This operation was based on the studies of Gray,i’ which showecl that the pectoral fascia was a plane practically devoid of- lymphatics, suggesting that lymphatics from the breast did not transgress the pectoral muscles en route to the axillary nodes. He reasoned that if the pectoral fascia could be stripped from the pectoral muscles and adequate axillary dissection could be doue, t.he operation would be as successful as radical mastectomy and less deforming. The ob-jections to this modihed radical mastectomy- were that exposure of the apex of the axilla was difficult and the axillary dissection wo~rld be less complete, the pectoralis major muscle would be denervated. and local recurrences would be increased. Subsecluent reported series have shown that the innervation of the pectoralis major can be preserved, that local recurrences are not increased, and tlte 5 and 10 year survival statistics are the same as those reported for radical mastectomy. Even if this operation resulted in a less complete dissection of the apex of the axilla. it would be unlikely that this would be reflected hy a decrease in patient survival, since, as .Auchinctoss”’ has shown, if’ a patient has more than four axillary tymph nodes involved, and especially if the apical axillary lymph nodes are involved, the prognosis is extremely poor anyhow. An even less extensive procedure for treatment of carcinoma of the breast is simple mastectomy comhinecl with postoperative irradiation. In 1948, McNThirter” published his results on a large series of women treated in this manner. McWhirter pointed out that surgical removal of the axillary contents is unnecessary il these tissues are not invaded by tumor and that, when they are involved. radical mastectomy often fails to cure the patient. Because of these facts. he reasoned that a new approach was.lustified. McUThirter was able TV) achieve a 50 per cent 10 year survival rate in his patients using simple mastectomy and radiotherapy. This over-all survival rate compared favorably with the results achieved bv radical mastectomv. McWhirter’s work has been criticized because some of his results were extrapolated to 5 year survivals, his dose of irradiation varieci, some of his patients were sublectect to oophorectomy, and some patients with persistent disease were treated with hormones. These criticisms notwithstanding~ other investigators have suhsecluently reported large series of patients treated by simple mastectomy and irradiation.“-” In
413
some of these series, patients have been retrospectively compared with similar patients treated bv t aclical mastectomy. While such studies are subject to the criticisms of any retrospective analysis, for the most part thev tend to support the concept that both the Yi ;tnd l&year survival rates for patients treated by simple mastectomy and irradiation are not statistically dif’ferent from the rates of those treated by radical master tomy. The least aggressive approach hn dwiing with a primary carcin(~m~i of the hreast i% that cbl’ remov-ing only the mass in the breast. Rentwed intcwst in the so-called lumpectomy operation began vvith the report of Adair18 in 1943. He utilized partial mastectomv in treating 53 patients, many of whom rweivecl preoperative and/or postoperative irradiation. ‘l’hc 5 vear survival rate in these patients was 70 per cent, Scwral authors have studied large gro~rps of’ pamws treated by lumpectomy and postoperative x-ray ~her:tp~. ‘The best results are those reported by Mustakallio.iS’ His series contained 127 patients with Stages 1 breast carcinoma. Eighty-four per cent of thew patiriit< stirvived for 5 years with 72 per cent surviving 10 vwrs. Crile and associateszO recentlv have reported a wries of 53 patients with 5 and 10 year survival rates oi. 77 and %I per cent. respectivelv.2” These alternate methods of therapy toi. primary breast carcinoma received further impettis with our increased knowledge of tumor biology. ~ltns ~~niversalty accepted fact that the present of nimot in regional nodes reduces the survival rate led to a clawit concept of tumor dissemination. A malignant tunior remains confined to its primary site for a period of time. When it metastasizes, it spreads first to the regwnal lymph nodes and. after a period of’ growth there. ciisseminatcs further to other locations. Thus, the principle of’ rcmoving the primary growth in continnitv with its lymphatic drainage wo~tld appear to of.fc i ttic patient the best chance of curt, We now know that the progression 01. the malignant tumor is not this simple. If it were rrw that breast carcinoma grew first in the regional ttc~des before dissemination. then all patients with ncgittive ivmph nodes should be cured of the disease, This is ncot the case, since 10 to 15 per cent of the patients with negative lymph nodes still succumb to the disease, Furthermore, Handley” showed that mow than 50 per cent of patients with inner quadrant and centrally located breast carcinomas who have positive. axillarv nodes also have positive internal mamntarv nodes, whereas positive intermu mammary nodes -arcsfound in only I8 per cent of patients with 0~itt.t quadrant lesions. If patients with central or inwr quadrant carcinomas were subjected to a standat-cl wlical mas-
tectomy, tumor would remain behind in the internal mammary nodes in more than 50 per cent of the cases. If this tumor subsequently metastasized to other parts of the body, the cure rate for cental and innerquadrant lesions should be much less than that for outer-quadrant lesions. Evidence seems to indicate that the survival rate in patients subjected to radical mastectomy is not influenced by the location of the primary tumor. Studies such as this have led investigators to reappraise this concept of tumor dissemination. The absence of tumor within lymph nodes may not mean that the tumor cells have remained confined to the primary growth, but rather that because of host resistance and/or tumor cell properties, disseminated cells are incapable of growth elsewhere in the body. Thus, the improved survival observed in patients with negative lymph nodes may be a reflection of a tumor-host relationship which inhibits the growth-disseminated tumor cells.*’ When one reviews the larger series of patients treated with these various methods of therapy, it is surprising to note the similarity of results. In almost all instances, regardless of the treatment employed, the 5 year cure rate for Stage 1 carcinoma of the breast is between 70 and 85 per cent. For Stage 2 carcinoma, the 5 year survival rate varies between 50 and 70 per cent. These survival rates have been interpreted by some as evidence that less extensive procedures are equally effective in treating carcinoma of the breast. However, several objections can be made to such inferences. Most of these studies are nonrandomized and are not prospective. Prospective randomization of patients is essential, for only in this manner can such variables as age, menstrual status, location of tumor, duration of the presence of tumor, size of tumor, and pathologic cell type be eliminated. Only when both the control group and the study group have large numbers of patients in each of these categories can adequate cornparisons be made. Frequently, survival statistics are quoted from studies in which the patients have not been staged at all or have been staged by the author’s own nonstandardized systems. When this occurs, it is impossible to tell whether the authors were highly selective in choosing only those patients who had a favorable prognosis for their procedure. Since accurate universally accepted standards of staging are now available, it is totally unacceptable for any author to present a series of cases which have not been staged according to accepted criteria. When lumpectomy is used as a treatment for primary breast cancer, the problem of multicentricity of the tumor must be considered. In 1969, Gallagher and
Marten,” studying 38 whole breast specimens, found that three fourths of the patients had other areas of the breast which were involved with either intraductal carcinoma, cellular hyperplasia, or epithelial atypism, and at least 50 per cent of these breasts had other sites of invasive carcinoma. They concluded, “all branches of a single nipple duct may be involved and this may be segmental or discontinuous.” Shah and associates” in 1973 found that 59 per cent of 508 patients who had an excisional biopsy of a malignant tumor prior to mastectomy still had carcinoma present in the mastectomy specimen. Studies such as this have made surgeons skeptical of an! treatment which does not remove all of the involved breast. Many studies show a surprisingly nonuniformity of treatment. Some of the patients have preoperative x-ray, others have postoperative x-ray; some patients have simple mastectomy with occasional enlarged nodes at the base of the axilla removed; some patients are treated with chemotherapy; others ha\,e undergone hormonal manipulations. In order for these studies to be adequately evaluated, the treatment IWSL be stanclardized in every patient. .4t the present time, \ve can say with certainty that those women in whom carcinoma of the breast is confined to the breast have a much better chance of survival than those women in whom tumor is found in the regional lymph nodes. The evidence for this is incontrovertible. However, several extremely important questions remained unanswered: (1) Does removal of the regional lymphatics improve survival when the tumor is clinically confined to the breast? (2) Does removal of the regional lymphatics improve survival when those lymphatics have been invaded by tumor? (3) If destruction of the regional lymphatics does improve survival, is x-ray therapy as effective as surgical removal? The national surgical adjuvant breast project, Protocol No. 4, is designed to answer these questions. Patients with Stage 1 carcinoma clinically confined LO the breast have been randomized into radical mastectomy, simple mastectomy alone, and simple mastectomy with irradiation. Patients with clinical Stage 2 carcinoma clinically involving the axillary lymph nodes are divided into radical mastectomy and simple mastectomy plus radiation therapy. Once large numbers of patients in each of these groups have been adequately studied for 10 vears, hopefully, \ve will have the answers IO these important unanswered questions. .4t the present time. what is the best advice a surgeon can give to his patients? With our current state of knowledge, removal of the breast and the axilkary contents appears to be the safest tnode of therapy.
Primary
Wher less radical procedures have never been shown to improve rhe survival rate. Whereas, some patients may do as we11 with lesser procedures, we are still unable to accurately identify these patients. The surgeon must merely exercise an educated guess as to which patients may be treated as successfully with a less radical procedure. Such a guess. even though it be an educated guess, subjects the patient tu undue risk ancf is not warranted. ‘IYhough the name of t-lalsted has become syncmymous with radical mastectomy, perhaps the statement with which he began his 1907 paper will ultimately prove to be his most valuable contribution: “It is cspeciallv true of’ breast cancer that the surgeon in-
treatment
of breast
carcinoma
415
terested in furnishing statistics may in perfectly honorable ways provide them. The most lwwicntiow man mav refuse to operate upon anv hut faw~&ie cases. and by performing an incomplete operation, t%xcludc from his list of complete operations suclt bad olws as hc finds himself operating upon.” This is an ~ldnloniti~~I1 to al1 c&us to remaiil skeptical. to challenge new tnocies of therapy, to refused E<)accept theory f’or f&t, and to design experimental and clinical studies which scientifically test new hypotheses. 0nly in this manner will changes in the ma~~agenlent of’ breast carcinoma be based less on emotion and mow on reason.
REFERENCES
f.
Hafsted,
W. S.: The
treatment
of wounds
with
especial
ref’erence to the value of the blood clot in the management of’ dead spaces, Johns Hopkins Hosp. Rep. 2: 255, 1890-9 I 2. Handle?, W. So: Cancer of. the breast and its operative treatment. London, 1907. W. Sampson. 3. Halsted, W. S.: The results of radical operations for the cure of carcinoma of the breast, Ann. Surg. 46: 1, 1907. 4. Haagensen, C. D., and Stout. A. P.: Carcinoma of the breast. II. tXteria operability. Ann. Surg. 118: 859, 1032, 1943. 5~ Haagensen, C. D., and O’Beid, S. G.: Biopsy of the apex of the axilfa in carcinoma of’ the breast, Ann. Surg. 149: 149, 1959. 6. Haagensen. C. II., and Coofey, E.: Radical mastectomy for ma~nmar~ carcinoma. Ann. Surg. 170: 884, 1969. i. Wangensteen, 0. H.: Superradical operation for breast cancer in the patient with fymph node involvement? Proc. Natl. Cancer Conf. 2: 230, 1952. 8. Kaae. S., ancf Johansen. H.: Breast cancer: Five year results, Am. J. Roentgenof. 87: 82, 1962. 9. Dahl-iversen, El., and Tobiassen, T.: Radical mastectolny with parasternal and supraclavicular dissection for mammary carcinoma, .knn Surg. 157: 170, 1963. f0. U&an. J. A.: What is the rationale for an extended radical procedure in eat-h cases? J. A. M. A. 199: 742, 1967. 11. Pate!, 11. H.* and Dyson. W. H.: The prognosis of carcinoma of’ the breast in relation to the type of operation performed, Br. J. Cancer 2: 7, 1948. f2. Grav. H. J.: Relation of rhe lymphatic vessels to the spread of cancer, Br. J. Surg. 26: 462, 1939, 13. ,Auchincfoss. H.: Significance of location and number of’ axiffary metastases in carcinoma of the breast: A justifica-
tion for 1963. 14. McWhirter, radiotherapy J* Radiof. 5. Williams, cinoma surgery,
a conservative
operation,
Ann.
Surg.
158:
37,
R.: The value of simple mastectomv and in the treatment of cat&r of’the brea& Br. 21: 599, 1948. J. G, Murley, R. S., and Curven, M. P.: Carof the female breast: Conservative radical Br. Med. J. 2: 787, 1953.
6. Kaae, S., and Johansen,
H.: Simple
mastectorn~ plus
postoperative irradiation by the method of McWhircer for mammary carcinoma, Prog. Cfin. Cancer I: 453. 1965. I 7. Brinkly, D., and Haybittfe, J. L.: Treatment of stage 11 carcinoma of the female breast, Lancer 2: 291, 1966. I& Adair, F‘ E.: The role of surgery and irracfiation in cancer of the breast, J.A.M.,% 121: 553, 1943. 19. Mustakallio, S.: Treatment of breast cancer by tumor extirpation and roentgen t.herapy instead of ra(fical operation, J. Fat. Radiol~ 6: 23, 1954.
20. Crile, G. Essefstyn, (1. EL, Herman, R. E.. and Hoerr, S 0.: Partial mastectomy for carcinoma of the hrczt, Surg. Gynecof. Obstet. 136: 929, 1973. 2 1. Handle?, R. S.: The early spread of breast c,arcinoma and its haring on operative treatment% Br. J. Sttrg~ 51: 206, 1964. 22. Fisher, B.: The surgical dilemma in the primary therapy of invasive breast cancer: A critical appraisaf, Curr. Probl. Surg. Oct. 1970. 23. Gallagher, H. S.. ancf Marten, J. I!,.: ‘Fhe sntdy of mammary carcinoma by mammography ancf whole organ sectioning, Cancer 23: 855, 1969, 24. Shah, J. P., Rosen, P. O., and Robbins, G. F.: Pitfalls of local excision in the treatment of carcinoma of the breast, Surg. Gynecof. Obstet. 136: 721, 1973.
Obstetrics and Gynecology ~dwne
126
number
CLINICAL
O~~I~~B~~:~
4
1.;.
I Slit5
OfWW3N
This section reports opinion on the handling of clinical situations, i.e., the clinica diagnosis and management of certain disease entities. Papers should range from eight to twenty typed pages, including illustrations, tables, and figures which clarif? the author’s management. References are limited to six citations. Mail to Frederick P. Zuspan, M.D., Editor.
The primary treatment of breast carcinoma STU.4RT
M.
POTICHz4,
M.D.
T/w major ~o~il~~tions in the surgical management of carcinoma of the breast hazv been re&wed. D&its in our current kndedge halIe been pointed out in an efjort to sepawte j&t jrom theory and so hdp the surgeon in choosing the best operation for ~1,&dent with breast ~ncer, THE PRIMARY treatment of breast carcinoma continues to be the subject of debate and controversy. Recent articles in both the medical and lay press have shaken traditional concepts, making it difficult for physicians to determine the proper treatment for a carcinoma of the breast. This indecision among physicians is further reflected in the growing number of patients who are reluctant to accept radical therapy. In this maze of conflicting views, how does the clinician reach a justifiable conclusion? The medical literature abounds with studies on the management of breast carcinoma and each method of therapy is supported by survival statistics. Although the strong advocate of a particular type of surgery can point out slight differences in both the 5 and 10 year survival rates by carefully selecting certain papers from the literature, the evidence so obtained cannot justifiably be used to prove the value of one procedure over another. A better understanding of the dilemma which faces (he surgeon may be obtained by reviewing the major contributions in the treatment of carcinoma of the
breast. In analyzing each procedure and the scientific evidence which supports it, the clinician begins to recognize what facts are known and what important questions remained unanswered. With this information, he may then plan a logical course of action in treating a patient with primary carcinoma of the breast. In 1890, William Stewart Halsted,’ reporting in the Bulletin of the, ,Johns Hopkins Ho,@tnl, described an operation for the treatment of carcinoma of I he breast which consisted of removing the entire breast. a liberal quantity of skin, all of the subcutaneous fat immediately overlying the breast tissue, the pet torahs major muscle (in later descriptions, the pectoralis minor muscle was also included), and all of the axillar! fat and lymphatics. The justification for such an extensive operation can be better appreciated when one considers Halsted’s concepts of the pathophysiology of metastasis from breast carcinoma. Halsted belielred that metastases from carcinoma of the breast lvere rarely disseminated through the venous system. He referred to Handley’s’ theory of centrifugal lymphatic spread in stating, “cancer of the breast preserves in lhc main continuity with the original growth and before in\,olving 411
the viscera may become widely diffused along surface planes.” Hatsted’s radical operation was based on tht premise that cure of even ad~.anwd carcinoma of the breast could be achieved by rcmova~ of’ the breast and aN of its contiguous tymphatics. He’ further postulated, ., so it is couceivabkz that ultimately. when out. knowledge of the tymphatics transversed in cases of’ femur involvement become sufficientty exact, amputation at the hip joint may seem incticated.” In 1907, Hatsted” reported the results of his operation. ‘Ilie cure rdte with negative axittary nodes was 70 per cent and his over-all GUI-c rate \vas 53.6 per cent of 2 10 cases. This operation became the unquestioned standard treatment for carcinoma of the breast for the next 50 years. Although some surgeons have argued that Hatsted’s reputation made others reluctant to question his operation, such criticism is unjustified. Undoubtedly, the first and most important reason for the success of this procedure was that Hatsted was able to cure 50 pw cent of women with carcinoma of the breast, whereas prior to his operation wry few had been cured. Halsted stated that, “. in this country at least a number of the leading surgeons of the generation prior to mine made the pronouncement that they had not in their lifetime cured a single case of breast cancer,” Second, radical mastectomy was associated with remarkably reproducible results. It was not an operation which could be successfully performed only at the .Johns Hopkins Hospital. other surgeons using this technique in centers throughout the worM soon rcported similar results. Third, the operation was safe. IHatsted’s hospital mortality rate was on])- I .7 per cent. In the 1940’s, several investigators began to question whether a radical mastectomy was the best operation for all women with carcinoma of the breast. This chattenge to such a traditional concept proceeded atong severat tines. Many surgeons concentrated their investigative efforts on refining the criteria for operability so as not to subject incurable women to extensive surgery. The most notabte studies in this regard are those of Haagensen and Stout.’ Beginning in 1943’ and culminating in 1959’ with a triple biopsy, Haagensen and his co-authors accurately defined operability in breast carcinoma. This screening technique included apical axiltary nodes and the internal mammary nodes in the first and second interspaces in addition to biopsy of the primary tumor. In this series of highly se&ted women treated by radical mastectomy, the 5 year survival rate was 85 per cent.’ As a corollary to this work. Haagensen and Cootey”
also described precise chnicat criteria for classil’\ illg carcinoma of the breast. ,4n accurate rncans of desc rilling breast tumors is essential to the surgicat management of this disease. Certaintv, if a surgeon is to gait) any knowledge from the reports of’ others? hc nlust know the precise nature of the tumors they are operaing upon. ‘rhe Columbia Classification described h\ Haagensen is one of’ the most popular systems currently used to ctassifv breast carcinomas: others include the .4merican system, the International system, and the Manchester system. White the differences in thehe classification systems are determined bv size of’ the primary tumor or the axillary metastasis, the major features are similar. Stage .4, or Stage I, consisw of carcinoma confined to the breast atone without anv ot the grave signs of extensive mahgnanc?. Stage B, OI Stage 2, wnsists of a similar primary tumor 11ith patpabte axittary lymph nodes. Stage C. or Stage 3. consists of a tumor which has one or more of the graw carcinoma, IMtlld~~ prognostic signs of advanced edema involving nlore than one third of the breast. fixation of the primary tumor to thy chest wall, ax&w!. lymph nodes greater than 2.5 cm. in diameter, or axillary lymph nodes hxed in the axitta. Suage 11, 01 Stage 4, consists of patients rvitti distant metastasis, A second group of investigators began to cxptore the advisability of extending the operation to include tymphatics ilot cnwmpassed in the standard radical mastectomy. ‘4tthough 1 19 of the 232 patients in Hatsted’s original series underwent a neck dissection, this part of’ the operation NX eventuath discontinued. Renewed interest in extended operations, M hich inch&d reseetion of the supractavicu~ar lymph Ilodes and resection of the internal mammary hmph nodes with or without resection of part of the chest wall, was stimulated by the work of Wagensteen,7 Kaae and Johansen,’ Dah~Iversen and Tofiassen,’ and Urban.“’ In general, these operations \\ere accompanied hy an increase in morbidity and mortality rates while not improving the survival rate to any appreciabIe degree. For the most part. these operations have again been abandoned. Some investigators still feet that the Urban operation, which removes the internal mammar? lymph nodes, is indicated in patients wilh centrali? located carcinomas or carcinomas arising in lhe inner quadrants of the breast. They reason that the increased morbidity is justified in these patients because of the high incidence of internal mammary node metastasis found with these lesions. Simuttaneously. other investigators began to examine the advisability of performing less extensive operations for the treatment of primar? carcinoma of the breast. These tess radical procedures included
Primary treatment of breast carcinoma
mod&d radical mastectomy< simple mastectomy, and subtotal mastectomy (lumpect~)my) with or without irradiation. In 1948* Patey and Dyson” described an operation which differed from the smndarcl radical mastectomy in that the pectoralis m+r muscle was not removed. ‘This operation was based on the studies of Gray,i’ which showecl that the pectoral fascia was a plane practically devoid of- lymphatics, suggesting that lymphatics from the breast did not transgress the pectoral muscles en route to the axillary nodes. He reasoned that if the pectoral fascia could be stripped from the pectoral muscles and adequate axillary dissection could be doue, t.he operation would be as successful as radical mastectomy and less deforming. The ob-jections to this modihed radical mastectomy- were that exposure of the apex of the axilla was difficult and the axillary dissection wo~rld be less complete, the pectoralis major muscle would be denervated. and local recurrences would be increased. Subsecluent reported series have shown that the innervation of the pectoralis major can be preserved, that local recurrences are not increased, and tlte 5 and 10 year survival statistics are the same as those reported for radical mastectomy. Even if this operation resulted in a less complete dissection of the apex of the axilla. it would be unlikely that this would be reflected hy a decrease in patient survival, since, as .Auchinctoss”’ has shown, if’ a patient has more than four axillary tymph nodes involved, and especially if the apical axillary lymph nodes are involved, the prognosis is extremely poor anyhow. An even less extensive procedure for treatment of carcinoma of the breast is simple mastectomy comhinecl with postoperative irradiation. In 1948, McNThirter” published his results on a large series of women treated in this manner. McWhirter pointed out that surgical removal of the axillary contents is unnecessary il these tissues are not invaded by tumor and that, when they are involved. radical mastectomy often fails to cure the patient. Because of these facts. he reasoned that a new approach was.lustified. McUThirter was able TV) achieve a 50 per cent 10 year survival rate in his patients using simple mastectomy and radiotherapy. This over-all survival rate compared favorably with the results achieved bv radical mastectomv. McWhirter’s work has been criticized because some of his results were extrapolated to 5 year survivals, his dose of irradiation varieci, some of his patients were sublectect to oophorectomy, and some patients with persistent disease were treated with hormones. These criticisms notwithstanding~ other investigators have suhsecluently reported large series of patients treated by simple mastectomy and irradiation.“-” In
413
some of these series, patients have been retrospectively compared with similar patients treated bv t aclical mastectomy. While such studies are subject to the criticisms of any retrospective analysis, for the most part thev tend to support the concept that both the Yi ;tnd l&year survival rates for patients treated by simple mastectomy and irradiation are not statistically dif’ferent from the rates of those treated by radical master tomy. The least aggressive approach hn dwiing with a primary carcin(~m~i of the hreast i% that cbl’ remov-ing only the mass in the breast. Rentwed intcwst in the so-called lumpectomy operation began vvith the report of Adair18 in 1943. He utilized partial mastectomv in treating 53 patients, many of whom rweivecl preoperative and/or postoperative irradiation. ‘l’hc 5 vear survival rate in these patients was 70 per cent, Scwral authors have studied large gro~rps of’ pamws treated by lumpectomy and postoperative x-ray ~her:tp~. ‘The best results are those reported by Mustakallio.iS’ His series contained 127 patients with Stages 1 breast carcinoma. Eighty-four per cent of thew patiriit< stirvived for 5 years with 72 per cent surviving 10 vwrs. Crile and associateszO recentlv have reported a wries of 53 patients with 5 and 10 year survival rates oi. 77 and %I per cent. respectivelv.2” These alternate methods of therapy toi. primary breast carcinoma received further impettis with our increased knowledge of tumor biology. ~ltns ~~niversalty accepted fact that the present of nimot in regional nodes reduces the survival rate led to a clawit concept of tumor dissemination. A malignant tunior remains confined to its primary site for a period of time. When it metastasizes, it spreads first to the regwnal lymph nodes and. after a period of’ growth there. ciisseminatcs further to other locations. Thus, the principle of’ rcmoving the primary growth in continnitv with its lymphatic drainage wo~tld appear to of.fc i ttic patient the best chance of curt, We now know that the progression 01. the malignant tumor is not this simple. If it were rrw that breast carcinoma grew first in the regional ttc~des before dissemination. then all patients with ncgittive ivmph nodes should be cured of the disease, This is ncot the case, since 10 to 15 per cent of the patients with negative lymph nodes still succumb to the disease, Furthermore, Handley” showed that mow than 50 per cent of patients with inner quadrant and centrally located breast carcinomas who have positive. axillarv nodes also have positive internal mamntarv nodes, whereas positive intermu mammary nodes -arcsfound in only I8 per cent of patients with 0~itt.t quadrant lesions. If patients with central or inwr quadrant carcinomas were subjected to a standat-cl wlical mas-
tectomy, tumor would remain behind in the internal mammary nodes in more than 50 per cent of the cases. If this tumor subsequently metastasized to other parts of the body, the cure rate for cental and innerquadrant lesions should be much less than that for outer-quadrant lesions. Evidence seems to indicate that the survival rate in patients subjected to radical mastectomy is not influenced by the location of the primary tumor. Studies such as this have led investigators to reappraise this concept of tumor dissemination. The absence of tumor within lymph nodes may not mean that the tumor cells have remained confined to the primary growth, but rather that because of host resistance and/or tumor cell properties, disseminated cells are incapable of growth elsewhere in the body. Thus, the improved survival observed in patients with negative lymph nodes may be a reflection of a tumor-host relationship which inhibits the growth-disseminated tumor cells.*’ When one reviews the larger series of patients treated with these various methods of therapy, it is surprising to note the similarity of results. In almost all instances, regardless of the treatment employed, the 5 year cure rate for Stage 1 carcinoma of the breast is between 70 and 85 per cent. For Stage 2 carcinoma, the 5 year survival rate varies between 50 and 70 per cent. These survival rates have been interpreted by some as evidence that less extensive procedures are equally effective in treating carcinoma of the breast. However, several objections can be made to such inferences. Most of these studies are nonrandomized and are not prospective. Prospective randomization of patients is essential, for only in this manner can such variables as age, menstrual status, location of tumor, duration of the presence of tumor, size of tumor, and pathologic cell type be eliminated. Only when both the control group and the study group have large numbers of patients in each of these categories can adequate cornparisons be made. Frequently, survival statistics are quoted from studies in which the patients have not been staged at all or have been staged by the author’s own nonstandardized systems. When this occurs, it is impossible to tell whether the authors were highly selective in choosing only those patients who had a favorable prognosis for their procedure. Since accurate universally accepted standards of staging are now available, it is totally unacceptable for any author to present a series of cases which have not been staged according to accepted criteria. When lumpectomy is used as a treatment for primary breast cancer, the problem of multicentricity of the tumor must be considered. In 1969, Gallagher and
Marten,” studying 38 whole breast specimens, found that three fourths of the patients had other areas of the breast which were involved with either intraductal carcinoma, cellular hyperplasia, or epithelial atypism, and at least 50 per cent of these breasts had other sites of invasive carcinoma. They concluded, “all branches of a single nipple duct may be involved and this may be segmental or discontinuous.” Shah and associates” in 1973 found that 59 per cent of 508 patients who had an excisional biopsy of a malignant tumor prior to mastectomy still had carcinoma present in the mastectomy specimen. Studies such as this have made surgeons skeptical of an! treatment which does not remove all of the involved breast. Many studies show a surprisingly nonuniformity of treatment. Some of the patients have preoperative x-ray, others have postoperative x-ray; some patients have simple mastectomy with occasional enlarged nodes at the base of the axilla removed; some patients are treated with chemotherapy; others ha\,e undergone hormonal manipulations. In order for these studies to be adequately evaluated, the treatment IWSL be stanclardized in every patient. .4t the present time, \ve can say with certainty that those women in whom carcinoma of the breast is confined to the breast have a much better chance of survival than those women in whom tumor is found in the regional lymph nodes. The evidence for this is incontrovertible. However, several extremely important questions remained unanswered: (1) Does removal of the regional lymphatics improve survival when the tumor is clinically confined to the breast? (2) Does removal of the regional lymphatics improve survival when those lymphatics have been invaded by tumor? (3) If destruction of the regional lymphatics does improve survival, is x-ray therapy as effective as surgical removal? The national surgical adjuvant breast project, Protocol No. 4, is designed to answer these questions. Patients with Stage 1 carcinoma clinically confined LO the breast have been randomized into radical mastectomy, simple mastectomy alone, and simple mastectomy with irradiation. Patients with clinical Stage 2 carcinoma clinically involving the axillary lymph nodes are divided into radical mastectomy and simple mastectomy plus radiation therapy. Once large numbers of patients in each of these groups have been adequately studied for 10 vears, hopefully, \ve will have the answers IO these important unanswered questions. .4t the present time. what is the best advice a surgeon can give to his patients? With our current state of knowledge, removal of the breast and the axilkary contents appears to be the safest tnode of therapy.
Primary
Wher less radical procedures have never been shown to improve rhe survival rate. Whereas, some patients may do as we11 with lesser procedures, we are still unable to accurately identify these patients. The surgeon must merely exercise an educated guess as to which patients may be treated as successfully with a less radical procedure. Such a guess. even though it be an educated guess, subjects the patient tu undue risk ancf is not warranted. ‘IYhough the name of t-lalsted has become syncmymous with radical mastectomy, perhaps the statement with which he began his 1907 paper will ultimately prove to be his most valuable contribution: “It is cspeciallv true of’ breast cancer that the surgeon in-
treatment
of breast
carcinoma
415
terested in furnishing statistics may in perfectly honorable ways provide them. The most lwwicntiow man mav refuse to operate upon anv hut faw~&ie cases. and by performing an incomplete operation, t%xcludc from his list of complete operations suclt bad olws as hc finds himself operating upon.” This is an ~ldnloniti~~I1 to al1 c&us to remaiil skeptical. to challenge new tnocies of therapy, to refused E<)accept theory f’or f&t, and to design experimental and clinical studies which scientifically test new hypotheses. 0nly in this manner will changes in the ma~~agenlent of’ breast carcinoma be based less on emotion and mow on reason.
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Hafsted,
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ref’erence to the value of the blood clot in the management of’ dead spaces, Johns Hopkins Hosp. Rep. 2: 255, 1890-9 I 2. Handle?, W. So: Cancer of. the breast and its operative treatment. London, 1907. W. Sampson. 3. Halsted, W. S.: The results of radical operations for the cure of carcinoma of the breast, Ann. Surg. 46: 1, 1907. 4. Haagensen, C. D., and Stout. A. P.: Carcinoma of the breast. II. tXteria operability. Ann. Surg. 118: 859, 1032, 1943. 5~ Haagensen, C. D., and O’Beid, S. G.: Biopsy of the apex of the axilfa in carcinoma of’ the breast, Ann. Surg. 149: 149, 1959. 6. Haagensen. C. II., and Coofey, E.: Radical mastectomy for ma~nmar~ carcinoma. Ann. Surg. 170: 884, 1969. i. Wangensteen, 0. H.: Superradical operation for breast cancer in the patient with fymph node involvement? Proc. Natl. Cancer Conf. 2: 230, 1952. 8. Kaae. S., ancf Johansen. H.: Breast cancer: Five year results, Am. J. Roentgenof. 87: 82, 1962. 9. Dahl-iversen, El., and Tobiassen, T.: Radical mastectolny with parasternal and supraclavicular dissection for mammary carcinoma, .knn Surg. 157: 170, 1963. f0. U&an. J. A.: What is the rationale for an extended radical procedure in eat-h cases? J. A. M. A. 199: 742, 1967. 11. Pate!, 11. H.* and Dyson. W. H.: The prognosis of carcinoma of’ the breast in relation to the type of operation performed, Br. J. Cancer 2: 7, 1948. f2. Grav. H. J.: Relation of rhe lymphatic vessels to the spread of cancer, Br. J. Surg. 26: 462, 1939, 13. ,Auchincfoss. H.: Significance of location and number of’ axiffary metastases in carcinoma of the breast: A justifica-
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R.: The value of simple mastectomv and in the treatment of cat&r of’the brea& Br. 21: 599, 1948. J. G, Murley, R. S., and Curven, M. P.: Carof the female breast: Conservative radical Br. Med. J. 2: 787, 1953.
6. Kaae, S., and Johansen,
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postoperative irradiation by the method of McWhircer for mammary carcinoma, Prog. Cfin. Cancer I: 453. 1965. I 7. Brinkly, D., and Haybittfe, J. L.: Treatment of stage 11 carcinoma of the female breast, Lancer 2: 291, 1966. I& Adair, F‘ E.: The role of surgery and irracfiation in cancer of the breast, J.A.M.,% 121: 553, 1943. 19. Mustakallio, S.: Treatment of breast cancer by tumor extirpation and roentgen t.herapy instead of ra(fical operation, J. Fat. Radiol~ 6: 23, 1954.
20. Crile, G. Essefstyn, (1. EL, Herman, R. E.. and Hoerr, S 0.: Partial mastectomy for carcinoma of the hrczt, Surg. Gynecof. Obstet. 136: 929, 1973. 2 1. Handle?, R. S.: The early spread of breast c,arcinoma and its haring on operative treatment% Br. J. Sttrg~ 51: 206, 1964. 22. Fisher, B.: The surgical dilemma in the primary therapy of invasive breast cancer: A critical appraisaf, Curr. Probl. Surg. Oct. 1970. 23. Gallagher, H. S.. ancf Marten, J. I!,.: ‘Fhe sntdy of mammary carcinoma by mammography ancf whole organ sectioning, Cancer 23: 855, 1969, 24. Shah, J. P., Rosen, P. O., and Robbins, G. F.: Pitfalls of local excision in the treatment of carcinoma of the breast, Surg. Gynecof. Obstet. 136: 721, 1973.