Cancer investigation, 10(5), 455-460 (1992)
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Indications for Breast Conservation in Early Stage Breast Cancer Peter I. Pressman, M.D. Department of Surgery, Mt. Sinai School of Medicine and Beth Israel and Lenox Hill Hospitals New York, New York
ABSTRACT Breast conservation, utilizing limited excisional breast surgery and axillary lymphadenectomy followed by radiation therapy can achieve excellent locall regional control and survival in many breust cancer patients. With average sized tumors, where larger volume resections are performed the results can equal that of the modified radical mastectomy. However, smaller tumors do very well with breast removal so it is a challenge to demonstrate that the long-term results of breast conservation in earlier stage disease ure equivalent to mustectomy. Small or occult tumors do not always indicate loculized disease and suitability for breast conservation depends on a combination qf factors: tumor size and ratio of tumor to breust volume, cell type, location of tumor, obtaining clear margins, the mammographic picture, multicentricity, and the probability of axillary lymph node involvement. It is important to se1ec.t patients for conservation where an equivalent survival can be expected. Recurrence in the rudiated breast usually is diagnosed and treated at a more advanced stage than the disease which was initially treated conservatively. It is dificult to manage and carries a poorer prognosis.
breast cancers are being diagnosed in earlier stages (1). This has been the goal of mass screening programs and it is being realized. The ultimate national impact of earlier detection on breast cancer statistics is still a long way
INTRODUCTION As the result of the increased availability of mammography and improvement in x-ray techniques, more 455
Copyright 0 1992 by Marcel Dekker. lnc.
Pressman
Cancer Invest Downloaded from informahealthcare.com by ThULB Jena on 11/12/14 For personal use only.
456
off since only 33% of women have had mammograms and the majority of women are not enrolled in yearly, routine studies ( 2 ) . As recently as 5 years ago only 23% of patients were diagnosed with in situ breast cancer. This has changed so dramatically that in 1991 between 20 and 25% of cancers were found at Stage 0, fewer in Stage 11, and the majority of cancers were diagnosed and treated in Stage I. In situ and localized (Stage I) breast cancer has the best rate of cure. With an increasing total number of breast cancers and a stable death rate, if all of the early stage breast cancers (including in situ disease) are included in the end results, this will translate into a remarkably higher improved survival and cure rate. Diagnosis at an earlier stage also has impacted importantly on the type of surgical procedures utilized to treat breast cancer. The radical mastectomy was necessary in the evolution of treatment of breast cancer 100 years ago. Before then, women had been treated for the complications of advanced breast malignancy-large breast masses, ulceration, bleeding, and pain. Introduction of the radical mastectomy (3) and its acceptance in the twentieth century made it possible to achieve not only local control of breast cancer, but also the first cures. Improvements in anesthesia and postoperative care increased the cure rates to a plateau which, however, remained relatively stationary for many decades. In the 1970s a number of factors converged to produce significant changes in the management of breast cancer in the United States. By far, the most important was the introduction of screening mammography. Breast cancers could be detected before they became apparent as clinical lumps. Where women were enrolled in screening programs, a 30% reduction in mortality was achieved and this has been sustained in 20 years of follow up (4). With the detection of smaller tumors came the opportunity to explore new approaches. The modified radical mastectomy, introduced in England in the 1950s, gradually began replacing the radical operation because of the activism of women and the willingness of a new generation of surgeons to abandon a monolithic approach to the disease. Preservation of the pectoralis major muscle in the modified operation and development of artificial prostheses made breast reconstruction feasible. In the 1980s the modified radical mastectomy supplanted the standard radical as the procedure of choice for operable breast cancer. Approaches to breast conservation were demonstrated to be as effective as mastectomy in treating operable breast cancer (5,6). As a result of this, most surgical residents in training today have never seen a Halsted radical mastectomy performed. By the end of the decade more than 50% of Stage I breast
cancers were treated with a nonmastectomy approach. At the NIH Consensus Development Conference in 1990 it was stated that “breast conservation is an appropriate method of primary therapy for the majority of women with Stage I and I1 breast cancer and is preferable because it provides survival equivalent to total mastectomy and axillary dissection while preserving the breast” (7). With this added imprimatur, it is likely that a higher percent of breast conserving operations will be performed than in the past. It is important to review what has been learned about the results and how they should impact on patient selection.
GOALS OF BREAST CANCER SURGERY When we talk about improving survival of patients with breast cancer, this can be accomplished in three different ways: 1. Earlier detection 2. Treatment at an earlier stage 3. Successful systemic adjuvant therapy Systemic therapy can convert locally advanced cancers into operable lesions, Stage 111 to Stage I1 disease. It can also successfully lengthen distant disease-free survival (DDFS) and survival (S) in women with positive axillary lymph nodes (8) and this advantage is also being reported with negative lymph nodes (9). Mammography is the only means of earlier detection. With the mammographic techniques of the 1960-197Os, finding impalpable tumors resulted in treating more Stage I cancers, fewer patients were diagnosed in Stage I1 and this translated into improved survival. There has always been concern that this might only reflect a longer lead time-treating earlier in the natural history of the disease and apparently producing a better survival, but ultimately not resulting in cure if patients are followed for a long enough time. This has proven not to be so-the survival advantage has persisted throughout 20 years of follow up. In addition to the HIP study, reports from the Netherlands and Scandinavia have supported this (10,ll). In more recent years, refinements in the techniques of mammography have additionally improved the detection of breast cancer in earlier stages-minimal disease which previously was encountered only rarely. In the United States in 1990, more than 22% of the breast cancers were diagnosed at an in situ stage. The mammographic findings today which most frequently motivate a breast biopsy are microcalcifications,
Breast Conservation in Early Stage Breast Cancer
subtle parenchymal distortions, and tiny masses. Needledirected biopsies are becoming the most common breast operations performed today. Breast cancer at the in situ stage is being sought and found in addition to the spectrum of infiltrating malignancies. Are all of these amenable to treatment with breast conservation? The principles of breast. cancer surgery as clearly stated by Dr. John Hayward remain the basis of sound treatment ( 12).
Cancer Invest Downloaded from informahealthcare.com by ThULB Jena on 11/12/14 For personal use only.
I. 2.
Treatment must ensure local control of disease It must supply sufficient tumor tissue for histological and biochemical analysis 3. It must be compatible with the use of adjuvant therapy 4. It must give full information on axillary node status The radical mastectomy accomplishes all of these goals and has correctly been the standard by which all other approaches are measured. The rates of local and regional recurrence and overall survival can be compared.
BREAST CONSERVATION Starting in I97 1, the U.S. National Surgical Adjuvant Breast and Bowel Project (NSABP) carried out a series of sequential studies to investigate lesser surgical procedures to determine whether these could replace radical mastectomy without affecting distant-disease-free survival (DDFS) and survival (S). Protocol B-04 (3) demonstrated that this could be accomplished without a radical mastectomy; the breast was removed, but the axillary lymph nodes were managed in different ways. When the axillary lymph nodes were not removed there were recurrences, albeit at a lower rate than anticipated. Protocol 8-06 ( 14) evaluated breast preservation and in the 2,000 women studied there was also no significant difference in DDFS or S. However, by 9 years 43% of the women treated by lumpectomy alone and 12% of those treated by lumpectomy and breast radiation did have recurrence in the treated breast. None of these approaches accomplished all of the principles previously enumerated. Obtaining local and regional control is important. Not only is recurrence of cancer in the retained breast or axillary lymph nodes an enormous disappointment for the patient, but. it can be extremely difficult to manage and impacts on survival where patients are followed long enough (15). The most impressive argument for the efficacy of breast conservation is the work of Veronesi et al. (16).
457 Where a quadrantectomy was combined with an axillary dissection and radiotherapy (QUART) for patients with tumors less than 2 cm in diameter, breast conservation was a safe alternative to mastectomy in terms of survival and local control of disease. There were 1232 patients treated and followed for approximately 7 years. Local recurrence of tumor was 4.3%. All of the principles enumerated were accomplished. This highly desirable result is not achieved with lumpectomy, with which it is often equated and misunderstood by both patients and physicians. Quadrantectomy is a radical operation involving removal of at least 2-3 cm of grossly normal tissue around the tumor, en bloc excision of the overlying skin of that quadrant of the breast, full thickness and including the underlying muscle fascia. Lumpectomy removes only a small rim of adjacent tissue-an excisional biopsy. Where such limited resections are performed the local recurrence rates are considerably higher. Veronesi et al. compared QUART with TART (tumorectomy, axillary dissection, and radiotherapy) in 705 patients (17). In a follow up of 3-5 years, the rate of local recurrence was I . 1 % with quadrantectomy versus 7.2% with lumpectomy. This did not impact on survival during this brief period. Comparing tumorectomy with wider excision, Ghossein reported that in 513 patients followed between 3 and 7 years, lumpectomy has a failure rate three times that of wider resection; 15% versus 5% (18). It is of particular interest that the wider resection in this study consisted of a 2 cm margin or greater where feasible, but, not a true quadrant. The results are equivalent to QUART. It is apparent that the best local control can be achieved when the largest volume of tissue is removed preliminary to radiotherapy Obtaining clear margins per se may not be statistically significant, but, the majority of patients with positive margins are in the lumpectomy group (19,20). In part, this may be related to the difficulty in interpreting specimens accurately. Most breast cancers have one margin at the anterior surface of the breast parenchyma so that unless the overlying skin is removed, even a tumor covered by a layer of fat looks like an involved margin when it reaches the pathology laboratory. Occasionally, I have found that where I excise an additional rim of tissue following excisional biopsy, the tumorectomy specimen will have negative margins, but, the concentric circle of adjacent tissue will contain microscopic malignancy. This is a reflection of the multifocal nature of breast cancer and is frequently related to the presence of a intraductal carcinoma associated with the infiltrating malignancy. Where this is present and the tumor has a high nuclear grade there is a considerable
Pressman
458
risk for recurrence; 39% versus 4% where these features were absent (2 1 1.
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HISTOLOGIC TYPE Infiltrating ductal and lobular carcinomas can both be treated with breast conservation where the clinically presenting mass is discrete. However, lobular carcinomas tend to be more diffuse and are generally larger masses when they are diagnosed and treated. These are more difficult to adequately widely excise and are frequently microscopically multicentric. This needs to be considered in planning a treatment approach and is one of the advantages in obtaining an excisional biopsy as an initial, separate procedure. Finding foci of infiltrating lobular carcinomas or lobular carcinomas in situ at the margins of a resection is a good indication that there is more disease which has not been encompassed by the tumorectomy and will be better treated by breast removal. It appears that there is a higher recurrence rate where patients with infiltrating lobular carcinoma are treated conservatively (22,23). These recurrences are also difficult to detect in the preserved breast, because, lobular carcinoma tends to infiltrate microscopically without producing either microcalcifications or desmoplastic reaction which are needed to be visualized on mammography. Since infiltrating lobular carcinomas exhibit the highest incidence of bilaterality, management of the opposite breast needs to be considered and these patients are candidates for prophylactic contralateral mastectomy.
OTHER FACTORS Cancers in noncontiguous locations in the breast generally contraindicate conservation because of the resulting poor cosmetic result. Volume is lost by wide excision and the additional radiation needed to boost two separate areas contributes to a poor cosmetic result. Two separate appearing cancers also should raise concern about what malignancy lurks between the two locations (24). Where nipple discharge is associated with the carcinoma or the tumor presents in a subareolar location, there is an inherent limitation in the feasibility of wide excision without sacrificing the nipple areolar complex. Malignancies arising in this precise area also obviously involve the ductal system. Where breast conservation with radiation therapy has been used for noninfiltrating lesions in this location, the results have been unacceptable (25). All other locations in the breast share equal outcomes.
Tumor size per se is not a contraindication to breast conservation. There is, however, an inherent problem in excising large tumors widely and retaining good COSmesis. Since the purpose of breast preservation is cosmetic, this is an important consideration. This does not infer that larger tumors in larger volume breasts cannot be treated conservatively. However, as larger tumors are treated, the incidence of lymph node involvement is higher and adequate axillary dissections are more difficult to accomplish via the small incisions used in conservation surgery. More aggressive axillary dissections translate into a higher incidence of arm and breast edema, particularly if it is necessary to radiate the axilla. In most published series there is a higher rate of recurrence in the breasts of women under 35 years of age who were treated conservatively (26,27) and a higher mortality. The reasons remain obscure.
RECURRENCES Recurrence on the chest wall after a mastectomy is a more serious event than a recurrence in the breast following conservation. Since these are probably different phenomena they shouldn’t be equated. The majority of post mastectomy recurrences are a harbinger of systemic metastatic disease whereas breast recurrences are more likely to be truly local. A mastectomy (salvage) is virtually always required to treat a relapse in the retained breast and the outcome is dependent on when this occurs. In a recent report from the New York Metropolitan Breast Cancer Group, 128 women with recurrences following conservation were studied. Early recurrences (less than 2 years following treatment) did much worse than women who had recurrences four or more years after conservation therapy. Where there were positive lymph nodes at the time of initial treatment the 5-year postsalvage rate was 35%. Overall relapse-free survival was 57% and overall survival was 65% (28). When breast reconstruction is carried out following a salvage mastectomy, a myocutaneous flap is usually needed because of the tissue changes due to prior radiation therapy.
EARLY STAGE BREAST CANCER Breast conservation should be recommended where the expectation of cure is that which can be accomplished with a modified radical mastectomy. It is true that current survival results are similar where patients are well selected for conservation and compared with mastectomy. We do not know what the results will be in 15 or more
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Breast Conservation in Early Stage Breast Cancer
years. The majority of these patients have Stage I and Stage 11 tumors and many of them will die of metastatic disease so the true breast recurrence rate is unknown. Recurrences after mastectomy are largely over by 10 years while in a retained breast, a steady rate of recurrence persists. This is either reappearance of the original malignancy or the occurrence of a new cancer in the breast. This risk will translate into loss of life for some women. Since mammograms are detecting earlier stage cancers in younger women there is a particular responsibility to select the modality of treatment wisely. Since these are women who should have a long survival, the risks of conservation should be minimal. It is important to carefully examine all parts of both breasts when treating a suspected unilateral breast cancer and to biopsy areas even of minimal clinical concern. The mammogram should similarly be scrutinized. Small densities or areas of microcalcifications, particularly apart from the major lesion, should be subjected to magnification for greater detail and biopsied. This can be accomplished with stereotaxic fine needle biopsy (29) more easily than with multiple, open operate procedures. The information learned can be of great value. Knowing that malignancy is present in two or more separate areas, contraindicates breast conservation.
459 4.
5.
6.
7. 8. 9. 10.
II
12. 13.
CONCLUSIONS 14.
Breast conservation can be utilized for early stage breast cancers with a high degree of safety and equivalence as regards local recurrence and survival in the relatively short-term follow-up reported. However, it is crucial to select wisely and avoid pitfalls which are predictive of local recurrences because these are difficult to manage and may contribute to mortality. There is a particular responsibility since mammography is detecting cancers in younger women where mastectomy has a known cure rate. Breast cancer continues to recur in the retained breast. albeit at a low rate.
15.
16.
17.
18.
REFERENCES 19. I . Robertson MR. Romanow J , Otchy DP, Walters MJ: Effect of
mass screening mammography on staging of carcinoma of the breast in women. Surg Gynecol Obstet 171:55-58. 1990. 2. NCI Breast Cancer Screening Consortium. Screening Mammography: A missed clinical opportunity? J Am Med Assoc 264(1):54-58. 1990. 3. Halsted WS. The results of radical operations for cure of cancer of the breast performed at the Johns Hopkins Hospital. Ann Surg 20:497, 1894.
20.
21.
Shapiro S , Venet W, Strax P et al: Selection. followup and analysis in the Health Insurance Plan study: A randomized trial with breast cancer screening. Natl Cancer Inst Monogr 67:65-74. 1985. Veronesi U , Saccozzi R, Del Vecchio M et al: Comparing radical mastectomy with quadrantectomy, axillary dissection and radiotherapy in patients with small cancers of the breast. N Eng J Med 305: 6-1 1, 1981. Fisher B, Bauer M, Margolese R et al. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of cancer. N Engl J Med 312:665-673. 1985. Treatment of Early Stage Breast Cancer. NIH Consensus Dev Conf Consensus Statement 1990 June 18-21:8(6). Henderson. 1C. Adjuvant systemic therapy: State ofthe art. 1989. Breast Ca Res and Treat 14:3-22, 1989. DeVita VT Jr. Breast Cancer Therapy: excercising our options. Edit. in N Engl J Med 320(8):529, 1989. Verbeek ALM, Hendricks JHCL, Holland R et al: Reduction of breast cancer mortality through mass screening with modern mammography: first results of the Nijmegen Project. 1975-1981. Lancet 1:1222-1224, 1984. Tabar L, Fagerbeg CJG, Gad A et al: Reduction mortality from breast cancer after mass screening with mammography: randomised trial from the breast cancer screening working group of the Swedish National Board of Health and Welfare. Lancet 1:829832, 1985. Hayward J, The principles of breast cancer surgery. Breast Cancer Res and Treat 4:61-68, 1984. Fisher B, Montague E. Redmond C et al. Comparison of radical mastectomy with alternative treatments for primary breast cancer: a first report of results from a prospective randomized clinical trial. Cancer 39:2827-39, 1977. Fisher B, Redmond C, Poisson R et al. Eight year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without radiation in the treatment of breast cancer. N Engl J Med 320:822-828. 1989. Osborne MP. Controversies in the management of primary breast cancer-a surgical analysis. Cancer Invest I (3):259-265. 1983. Veronesi U, Salvadori B, Luini A et al: Conservative treatment of early breast cancer. Long term results of 1232 cases treated with quadrantectomy, axillary dissection and radiotherapy. Ann Surg 21 1:250-259. 1990. Veronesi U, Volterrani F. Luini A et al: Quadrantectomy versus lumpectomy for small size breast cancer. Eur J Cancer 26(6): 671-673, 1990. Ghossein NA, Alpert S , Barba J et al: Importance of adequate surgical excision prior to radiotherapy in the local control of patients treated conservatively for breast cancer. Arch Surg 127:411-415, 1992. Ghossein NA, Vilcoq JR. Stacey P, Calle R: Conservation surgery and radiotherapy in the treatment of localized breast cancer. A retrospective analysis. Front Radiat Ther Onc 17: 102-109. 1983. Veronesi U: Breast conservation trials of the NCI-Milam in early Stage breast cancer. NIH Consens Dev Conf. National Institutes of Health. Bethesda, MD, June 18-21, 1990. Schmitt SJ. Connolly JL. Harris JR, Hellman S . Cohen R: Pathologic predictors of early recurrence in Stage I and 11 breast cancer treated by primary radiation therapy. Cancer 53: 1049-1057. 1984.
460 Schnitt SJ, Connolly JL, Silver B et al: Infiltrating lobular carcinoma of the breast: Results of treatment with conservative surgery (S) and radiotherapy (RT) (abstr). Int J Radiat Oncol Biol Phys 15 (supp. I ) : 194, 1988. 23. Kurtz JM, Jacquemier J , Torhorst J et al: Conservation therapy for breast cancers other than infiltrating ductal carcinoma. Cancer 63: 1630- 1635. 1989. 24. Leopold KA. Recht A, Schnitt SJ et al: Results of conservative surgery and radiation therapy for multiple synchronous cancers of one breast. Int J Rad Oncol Biol Phys 16:11-16, 1989. 25. Recht A, Harris JR: Selection of patients with early stage breast cancer for conservative surgery and radiation. Oncology 4(2):2332, 1990.
Cancer Invest Downloaded from informahealthcare.com by ThULB Jena on 11/12/14 For personal use only.
22.
Pressman 26.
Boyages J, Recht A, Connolly J et al: Factors associated with local recurrence as a first site of failure following the conservative treatment of early breast cancer (abstr). Int J Radiat Oncol Biol Phys 15 (sup. I): 181-182, 1988. 27. Calle R, Vilcoq JR, Zafrani B, Vielh P, Fouquet A. Local control and survival of breast cancer treated by limited surgery followed by irradiation. Cancer 122373-878, 1986. 28. Osbome MP, Borgen P, Wong G et al. Salvage mastectomy study, New York Metropolitan Breast Cancer Group. (Abst) American Radium Society, May 1991, Montreal, Canada. 29. Mitnick J , Vazquez M, Roses D et al: Stereotaxic localization for fine-needle aspiration breast biopsy. Arch Surg 126:1 1371140, 1991.
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Indications for Breast Conservation in Early Stage Breast Cancer Peter I. Pressman, M.D. Department of Surgery, Mt. Sinai School of Medicine and Beth Israel and Lenox Hill Hospitals New York, New York
ABSTRACT Breast conservation, utilizing limited excisional breast surgery and axillary lymphadenectomy followed by radiation therapy can achieve excellent locall regional control and survival in many breust cancer patients. With average sized tumors, where larger volume resections are performed the results can equal that of the modified radical mastectomy. However, smaller tumors do very well with breast removal so it is a challenge to demonstrate that the long-term results of breast conservation in earlier stage disease ure equivalent to mustectomy. Small or occult tumors do not always indicate loculized disease and suitability for breast conservation depends on a combination qf factors: tumor size and ratio of tumor to breust volume, cell type, location of tumor, obtaining clear margins, the mammographic picture, multicentricity, and the probability of axillary lymph node involvement. It is important to se1ec.t patients for conservation where an equivalent survival can be expected. Recurrence in the rudiated breast usually is diagnosed and treated at a more advanced stage than the disease which was initially treated conservatively. It is dificult to manage and carries a poorer prognosis.
breast cancers are being diagnosed in earlier stages (1). This has been the goal of mass screening programs and it is being realized. The ultimate national impact of earlier detection on breast cancer statistics is still a long way
INTRODUCTION As the result of the increased availability of mammography and improvement in x-ray techniques, more 455
Copyright 0 1992 by Marcel Dekker. lnc.
Pressman
Cancer Invest Downloaded from informahealthcare.com by ThULB Jena on 11/12/14 For personal use only.
456
off since only 33% of women have had mammograms and the majority of women are not enrolled in yearly, routine studies ( 2 ) . As recently as 5 years ago only 23% of patients were diagnosed with in situ breast cancer. This has changed so dramatically that in 1991 between 20 and 25% of cancers were found at Stage 0, fewer in Stage 11, and the majority of cancers were diagnosed and treated in Stage I. In situ and localized (Stage I) breast cancer has the best rate of cure. With an increasing total number of breast cancers and a stable death rate, if all of the early stage breast cancers (including in situ disease) are included in the end results, this will translate into a remarkably higher improved survival and cure rate. Diagnosis at an earlier stage also has impacted importantly on the type of surgical procedures utilized to treat breast cancer. The radical mastectomy was necessary in the evolution of treatment of breast cancer 100 years ago. Before then, women had been treated for the complications of advanced breast malignancy-large breast masses, ulceration, bleeding, and pain. Introduction of the radical mastectomy (3) and its acceptance in the twentieth century made it possible to achieve not only local control of breast cancer, but also the first cures. Improvements in anesthesia and postoperative care increased the cure rates to a plateau which, however, remained relatively stationary for many decades. In the 1970s a number of factors converged to produce significant changes in the management of breast cancer in the United States. By far, the most important was the introduction of screening mammography. Breast cancers could be detected before they became apparent as clinical lumps. Where women were enrolled in screening programs, a 30% reduction in mortality was achieved and this has been sustained in 20 years of follow up (4). With the detection of smaller tumors came the opportunity to explore new approaches. The modified radical mastectomy, introduced in England in the 1950s, gradually began replacing the radical operation because of the activism of women and the willingness of a new generation of surgeons to abandon a monolithic approach to the disease. Preservation of the pectoralis major muscle in the modified operation and development of artificial prostheses made breast reconstruction feasible. In the 1980s the modified radical mastectomy supplanted the standard radical as the procedure of choice for operable breast cancer. Approaches to breast conservation were demonstrated to be as effective as mastectomy in treating operable breast cancer (5,6). As a result of this, most surgical residents in training today have never seen a Halsted radical mastectomy performed. By the end of the decade more than 50% of Stage I breast
cancers were treated with a nonmastectomy approach. At the NIH Consensus Development Conference in 1990 it was stated that “breast conservation is an appropriate method of primary therapy for the majority of women with Stage I and I1 breast cancer and is preferable because it provides survival equivalent to total mastectomy and axillary dissection while preserving the breast” (7). With this added imprimatur, it is likely that a higher percent of breast conserving operations will be performed than in the past. It is important to review what has been learned about the results and how they should impact on patient selection.
GOALS OF BREAST CANCER SURGERY When we talk about improving survival of patients with breast cancer, this can be accomplished in three different ways: 1. Earlier detection 2. Treatment at an earlier stage 3. Successful systemic adjuvant therapy Systemic therapy can convert locally advanced cancers into operable lesions, Stage 111 to Stage I1 disease. It can also successfully lengthen distant disease-free survival (DDFS) and survival (S) in women with positive axillary lymph nodes (8) and this advantage is also being reported with negative lymph nodes (9). Mammography is the only means of earlier detection. With the mammographic techniques of the 1960-197Os, finding impalpable tumors resulted in treating more Stage I cancers, fewer patients were diagnosed in Stage I1 and this translated into improved survival. There has always been concern that this might only reflect a longer lead time-treating earlier in the natural history of the disease and apparently producing a better survival, but ultimately not resulting in cure if patients are followed for a long enough time. This has proven not to be so-the survival advantage has persisted throughout 20 years of follow up. In addition to the HIP study, reports from the Netherlands and Scandinavia have supported this (10,ll). In more recent years, refinements in the techniques of mammography have additionally improved the detection of breast cancer in earlier stages-minimal disease which previously was encountered only rarely. In the United States in 1990, more than 22% of the breast cancers were diagnosed at an in situ stage. The mammographic findings today which most frequently motivate a breast biopsy are microcalcifications,
Breast Conservation in Early Stage Breast Cancer
subtle parenchymal distortions, and tiny masses. Needledirected biopsies are becoming the most common breast operations performed today. Breast cancer at the in situ stage is being sought and found in addition to the spectrum of infiltrating malignancies. Are all of these amenable to treatment with breast conservation? The principles of breast. cancer surgery as clearly stated by Dr. John Hayward remain the basis of sound treatment ( 12).
Cancer Invest Downloaded from informahealthcare.com by ThULB Jena on 11/12/14 For personal use only.
I. 2.
Treatment must ensure local control of disease It must supply sufficient tumor tissue for histological and biochemical analysis 3. It must be compatible with the use of adjuvant therapy 4. It must give full information on axillary node status The radical mastectomy accomplishes all of these goals and has correctly been the standard by which all other approaches are measured. The rates of local and regional recurrence and overall survival can be compared.
BREAST CONSERVATION Starting in I97 1, the U.S. National Surgical Adjuvant Breast and Bowel Project (NSABP) carried out a series of sequential studies to investigate lesser surgical procedures to determine whether these could replace radical mastectomy without affecting distant-disease-free survival (DDFS) and survival (S). Protocol B-04 (3) demonstrated that this could be accomplished without a radical mastectomy; the breast was removed, but the axillary lymph nodes were managed in different ways. When the axillary lymph nodes were not removed there were recurrences, albeit at a lower rate than anticipated. Protocol 8-06 ( 14) evaluated breast preservation and in the 2,000 women studied there was also no significant difference in DDFS or S. However, by 9 years 43% of the women treated by lumpectomy alone and 12% of those treated by lumpectomy and breast radiation did have recurrence in the treated breast. None of these approaches accomplished all of the principles previously enumerated. Obtaining local and regional control is important. Not only is recurrence of cancer in the retained breast or axillary lymph nodes an enormous disappointment for the patient, but. it can be extremely difficult to manage and impacts on survival where patients are followed long enough (15). The most impressive argument for the efficacy of breast conservation is the work of Veronesi et al. (16).
457 Where a quadrantectomy was combined with an axillary dissection and radiotherapy (QUART) for patients with tumors less than 2 cm in diameter, breast conservation was a safe alternative to mastectomy in terms of survival and local control of disease. There were 1232 patients treated and followed for approximately 7 years. Local recurrence of tumor was 4.3%. All of the principles enumerated were accomplished. This highly desirable result is not achieved with lumpectomy, with which it is often equated and misunderstood by both patients and physicians. Quadrantectomy is a radical operation involving removal of at least 2-3 cm of grossly normal tissue around the tumor, en bloc excision of the overlying skin of that quadrant of the breast, full thickness and including the underlying muscle fascia. Lumpectomy removes only a small rim of adjacent tissue-an excisional biopsy. Where such limited resections are performed the local recurrence rates are considerably higher. Veronesi et al. compared QUART with TART (tumorectomy, axillary dissection, and radiotherapy) in 705 patients (17). In a follow up of 3-5 years, the rate of local recurrence was I . 1 % with quadrantectomy versus 7.2% with lumpectomy. This did not impact on survival during this brief period. Comparing tumorectomy with wider excision, Ghossein reported that in 513 patients followed between 3 and 7 years, lumpectomy has a failure rate three times that of wider resection; 15% versus 5% (18). It is of particular interest that the wider resection in this study consisted of a 2 cm margin or greater where feasible, but, not a true quadrant. The results are equivalent to QUART. It is apparent that the best local control can be achieved when the largest volume of tissue is removed preliminary to radiotherapy Obtaining clear margins per se may not be statistically significant, but, the majority of patients with positive margins are in the lumpectomy group (19,20). In part, this may be related to the difficulty in interpreting specimens accurately. Most breast cancers have one margin at the anterior surface of the breast parenchyma so that unless the overlying skin is removed, even a tumor covered by a layer of fat looks like an involved margin when it reaches the pathology laboratory. Occasionally, I have found that where I excise an additional rim of tissue following excisional biopsy, the tumorectomy specimen will have negative margins, but, the concentric circle of adjacent tissue will contain microscopic malignancy. This is a reflection of the multifocal nature of breast cancer and is frequently related to the presence of a intraductal carcinoma associated with the infiltrating malignancy. Where this is present and the tumor has a high nuclear grade there is a considerable
Pressman
458
risk for recurrence; 39% versus 4% where these features were absent (2 1 1.
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HISTOLOGIC TYPE Infiltrating ductal and lobular carcinomas can both be treated with breast conservation where the clinically presenting mass is discrete. However, lobular carcinomas tend to be more diffuse and are generally larger masses when they are diagnosed and treated. These are more difficult to adequately widely excise and are frequently microscopically multicentric. This needs to be considered in planning a treatment approach and is one of the advantages in obtaining an excisional biopsy as an initial, separate procedure. Finding foci of infiltrating lobular carcinomas or lobular carcinomas in situ at the margins of a resection is a good indication that there is more disease which has not been encompassed by the tumorectomy and will be better treated by breast removal. It appears that there is a higher recurrence rate where patients with infiltrating lobular carcinoma are treated conservatively (22,23). These recurrences are also difficult to detect in the preserved breast, because, lobular carcinoma tends to infiltrate microscopically without producing either microcalcifications or desmoplastic reaction which are needed to be visualized on mammography. Since infiltrating lobular carcinomas exhibit the highest incidence of bilaterality, management of the opposite breast needs to be considered and these patients are candidates for prophylactic contralateral mastectomy.
OTHER FACTORS Cancers in noncontiguous locations in the breast generally contraindicate conservation because of the resulting poor cosmetic result. Volume is lost by wide excision and the additional radiation needed to boost two separate areas contributes to a poor cosmetic result. Two separate appearing cancers also should raise concern about what malignancy lurks between the two locations (24). Where nipple discharge is associated with the carcinoma or the tumor presents in a subareolar location, there is an inherent limitation in the feasibility of wide excision without sacrificing the nipple areolar complex. Malignancies arising in this precise area also obviously involve the ductal system. Where breast conservation with radiation therapy has been used for noninfiltrating lesions in this location, the results have been unacceptable (25). All other locations in the breast share equal outcomes.
Tumor size per se is not a contraindication to breast conservation. There is, however, an inherent problem in excising large tumors widely and retaining good COSmesis. Since the purpose of breast preservation is cosmetic, this is an important consideration. This does not infer that larger tumors in larger volume breasts cannot be treated conservatively. However, as larger tumors are treated, the incidence of lymph node involvement is higher and adequate axillary dissections are more difficult to accomplish via the small incisions used in conservation surgery. More aggressive axillary dissections translate into a higher incidence of arm and breast edema, particularly if it is necessary to radiate the axilla. In most published series there is a higher rate of recurrence in the breasts of women under 35 years of age who were treated conservatively (26,27) and a higher mortality. The reasons remain obscure.
RECURRENCES Recurrence on the chest wall after a mastectomy is a more serious event than a recurrence in the breast following conservation. Since these are probably different phenomena they shouldn’t be equated. The majority of post mastectomy recurrences are a harbinger of systemic metastatic disease whereas breast recurrences are more likely to be truly local. A mastectomy (salvage) is virtually always required to treat a relapse in the retained breast and the outcome is dependent on when this occurs. In a recent report from the New York Metropolitan Breast Cancer Group, 128 women with recurrences following conservation were studied. Early recurrences (less than 2 years following treatment) did much worse than women who had recurrences four or more years after conservation therapy. Where there were positive lymph nodes at the time of initial treatment the 5-year postsalvage rate was 35%. Overall relapse-free survival was 57% and overall survival was 65% (28). When breast reconstruction is carried out following a salvage mastectomy, a myocutaneous flap is usually needed because of the tissue changes due to prior radiation therapy.
EARLY STAGE BREAST CANCER Breast conservation should be recommended where the expectation of cure is that which can be accomplished with a modified radical mastectomy. It is true that current survival results are similar where patients are well selected for conservation and compared with mastectomy. We do not know what the results will be in 15 or more
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Breast Conservation in Early Stage Breast Cancer
years. The majority of these patients have Stage I and Stage 11 tumors and many of them will die of metastatic disease so the true breast recurrence rate is unknown. Recurrences after mastectomy are largely over by 10 years while in a retained breast, a steady rate of recurrence persists. This is either reappearance of the original malignancy or the occurrence of a new cancer in the breast. This risk will translate into loss of life for some women. Since mammograms are detecting earlier stage cancers in younger women there is a particular responsibility to select the modality of treatment wisely. Since these are women who should have a long survival, the risks of conservation should be minimal. It is important to carefully examine all parts of both breasts when treating a suspected unilateral breast cancer and to biopsy areas even of minimal clinical concern. The mammogram should similarly be scrutinized. Small densities or areas of microcalcifications, particularly apart from the major lesion, should be subjected to magnification for greater detail and biopsied. This can be accomplished with stereotaxic fine needle biopsy (29) more easily than with multiple, open operate procedures. The information learned can be of great value. Knowing that malignancy is present in two or more separate areas, contraindicates breast conservation.
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CONCLUSIONS 14.
Breast conservation can be utilized for early stage breast cancers with a high degree of safety and equivalence as regards local recurrence and survival in the relatively short-term follow-up reported. However, it is crucial to select wisely and avoid pitfalls which are predictive of local recurrences because these are difficult to manage and may contribute to mortality. There is a particular responsibility since mammography is detecting cancers in younger women where mastectomy has a known cure rate. Breast cancer continues to recur in the retained breast. albeit at a low rate.
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