Breast Conservation Management of Breast Tumors 4 cm or Larger Khanna, MD; Rufus J. Mark, MD; Melvin J. Silverstein, MD; Guy Juillard, MD; Bernard Lewinsky, MD; Armando E. Giuliano, MD

Monica M.

\s=b\ Randomized studies of stage I and II breast cancer have shown that breast conservation treatment is equivalent to modified radical mastectomy in regard to local-regional control and survival. Little has been published on breast conservation for patients with large tumors. We analyzed 68 patients with tumors measuring 4 cm or larger (range, 4 to 12 cm) treated with breast-conserving surgery and radiation therapy. The median follow-up was 46 months; the mean tumor size was 5 cm. The 5-year actuarial localregional recurrence rate was 8.5%, and the overall survival and disease-free survival rates were 76% and 68%, respectively. We conclude that breast conservation treatment may be a reasonable alternative to mastectomy in patients with tumors 4 cm or larger without compromise in local-regional control or survival, while achieving acceptable cosmesis.

conservation management for treatment of breast cancer have found no difference in outcome when primary tumor size and local relapse have been examined.5-6'911 However, there also exists information in the medical literature to the contrary. In 1989, a study in the British Journal ofSurgery cited that an increase in local recurrence was found with tumors larger than 2 cm after treatment with conservation manage¬ ment. The authors concluded that patients with tumors larger than 3 cm should undergo mastectomy.12 In June 1990, the National Institutes of Health Consensus Development Conference on early-stage breast cancer stated that breast conservation management for stage I and II breast cancer was appropriate, but also stated that in general, the risk of recurrence increases as tumor size increases.13 The purpose of this study is to examine the management and outcome of patients with large T2 and T3 tumors treated with breast-conserving surgery and radiation therapy.

randomized trials have clearly established Prospecti v e that breast-conserving postoperative and diation for equivalent

MATERIALS AND METHODS We examined medical records of patients who were treated with local tumor excision followed by radiation therapy at the UCLA, the Western Tumor Medical Group, Van Nuys, Calif, or The Breast Center, Van Nuys, between 1978 and 1990. Those pa¬ tients whose tumors were 4 cm or larger were studied. Prognos¬ tic factors examined were tumor size, histologie characteristics, lymph node status, surgical margin status, age, and use of adju¬ vant chemotherapy. Examination for an extensive intraductal component within the tumor was not performed. Tumor size was determined from the record of the physical examination by the examining physician or from the gross description documented in the pathology report. The histologie characteristics, lymph node status, and surgical margin status were obtained from the

(Arch Surg. 1992;127:1038-1043)

ra¬ surgery and breast cancer II I to are stage as as in well control local-regional mastectomy achieving overall survival and disease-free survival.14 The largest prospective randomized trial of conservative surgery and radiation therapy is the National Surgical Adjuvant Breast Project B-06 trial in which patients with tumors of up to 4 cm were eligible. Those with tumors larger than 4 cm were excluded from this trial and have traditionally undergone mastectomy. The incidence of local recurrence for patients with stage I and II breast cancer treated with breast-conserving surgery and postoperative radiation ranges from 5% to 10% at 5 years. Longer follow-up data are available that define the local recurrence rate of approximately 10% to 15% at 10 years.5"8 Investigators of several retrospective studies on breast

Accepted for publication June 6,

1992.

Department of Radiation Oncology, UCLA (Drs Khanna and Juillard); the Radiation Medical Group, San Diego, Calif (Dr Mark); the Department of Surgery, The Breast Center, Van Nuys, Calif (Dr Silverstein); the Western Tumor Medical Group, Van Nuys (Dr Lewinsky); and The John Wayne Cancer Institute at Saint John's Hospital, Santa Monica, From the

Calif (Dr Giuliano). Presented at the 63rd Annual

Meeting of the Pacific

Coast

Surgical

Association, Kauai, Hawaii, February 18, 1992. Reprint requests to Department of Radiation Oncology, UCLA, 200 Medical Plaza, Los Angeles, CA 90024 (Dr Khanna).

pathology report. In general, operation was performed by widely excising either the primary tumor or the biopsy site with a rim of normalappearing breast tissue to obtain tumor-free margins, as advo¬ cated in the National Surgical Adjuvant Breast Project B-06 pro¬ tocol.1 Axillary node dissection was performed by resecting at least level I and II lymph nodes. In general, postoperative radio¬ therapy consisted of treatment of the entire breast with tangen¬ tial fields to a total dose of 4500 to 5040 cGy delivered in 180- to 200-cGy fractions over a period of 4'/2 to 51/2 weeks. The regional nodes were irradiated to a total dose of 4500 cGy, when indicated. The patients in this study were treated by a number of different surgeons and radiation oncologists. Cosmesis was assessed by the patient and physician. For phy¬

sician examination, an "excellent" score was recorded when the treated breast was almost identical to the untreated breast. A score

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Table 1.—Distribution of Patients and Recurrence Rate

vs

Local-Regional

Tumor Size

No. (%) of No. of

Tumor

Diameter,

cm

Patients

Local-Regional Recurrences

4.0-4.9

32

2 (6.3)

5.0-5.9

18

1 (5.6)

6.0-6.9

10

7.0-7.9

3

0

8.0-12.0

5

1 (20)

Table

1 (10)

Between Surgical Margin 2.—Relationship and Local Status

Recurrence

No. (%) No. of Patients

Recurrence

Positive

15

3(20)

Negative

38

0

Unknown

15

1 (7)

Margin Status

With Local

of "good" was recorded when some slight differences were noted between the two breasts. A "fair" result indicated obvious differ¬ ences between the two breasts, and a "poor" cosmetic result in¬ dicated marked distortion of the treated breast. Patients were simply asked to evaluate cosmesis. Local-regional recurrence was defined as recurrence of cancer in the treated breast or regional lymph nodes occurring with or without the diagnosis of distant métastases. We used the onset of definitive surgery as the initiation point for follow-up. The length of follow-up was determined by the date of last contact with a physician or the date of the patient's death. The median follow-up of patients was 46 months (range, 4 to 139 months). The results are presented in terms of local-regional recurrence, overall survival and disease-free survival rates, and cosmesis.

1.—Overall (upper curve) and disease-free (lower curve) survival for all patients. Percentages for overall survival were derived from totals of 57, 39, and22 patients at risk at 20, 40, and 60 months, respec¬ tively; percentages for disease-free survival were derived from totals of 54, 35, and 19 patients at risk at 20, 40, and 60 months, respectively.

Fig

rates

Local-regional recurrence is analyzed in regard to tumor size, surgical margin status, lymph node status, and use of adjuvant chemotherapy. Survival curves and actuarial rates are calculated using the Kaplan-Meier method.14

RESULTS with tumors 4 cm or larger were Sixty-eight patients studied. The mean tumor size was 5.0 cm, with 88% of the patients having tumors of less than 7 cm. The 5-year actu¬ arial local-regional recurrence rate was 8.5% (SE, ±4%). Local-regional recurrence developed in five patients: four in the ipsilateral breast and one in the axilla. Three (6%) of 50 patients with local recurrences had lesions measuring 4.0 to 5.9 cm, compared with two (11%) of 18 patients with tumors measuring 6 cm or larger (Table 1). Two patients with recurrences in the breast underwent mastectomy and were rendered free of disease. The third patient with recurrence in the breast achieved local control following mastectomy but subsequently developed distant mé¬ tastases. The remaining two patients with local-regional recurrences had distant métastases at the time of local-

regional recurrence. Local-regional recurrences developed

within 38 months in four patients, and at 78 months in the fifth patient. Margin status was not known in 15 patients, positive in another 15 patients, and negative in 38 patients. Among our four patients with recurrences in the breast, there were three positive margins of resection and one unknown margin of resection. Therefore, among the 15 patients with

Fig 2.—Cosmetic result of patient who had a 4-cm outer quadrant of the left breast.

tumor in

the upper

positive surgical margins, three (20%) had local recurrence, as opposed to one (7%) of 15 patients with unknown mar¬ gins. There were no local recurrences in the patients with negative margins of resection (Table 2). All patients in whom margin status was not known had undergone op¬

eration before 1985. Axillary node dissection was performed in 64 patients. Of these, lymph node involvement was found in 28 patients (44%). Only one of the five local-regional recur¬ rences occurred in a patient with axillary lymph node in¬ volvement. Equal numbers of patients were premenopausal and postmenopausal; the ages ranged between 23 and 84 years (mean age, 50 years). We found that the his¬ tologie features and age of the patient were not important

prognostic factors influencing local-regional recurrence. Thirty-nine (57%) of the 68 patients received adjuvant chemotherapy, of which 23 patients (59%) had positive nodes. Adjuvant ministered either concurrently or

axillary lymph

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chemotherapy was ad¬ sequentially with radia-

Several

of chemotherapy were being cyclophosphamide (Cytoxan), methotrexate sodium, and fluorouracil and cyclo¬ phosphamide, doxorubicin hydrochloride (Adriamycin), tion

therapy.

used, the

most

regimens

common

and fluorouracil. Local recurrence occurred in two (5%) of 39 patients who received adjuvant chemotherapy and in two (7%) of 29 who did not. In this study, actuarial overall survival and disease-free survival rates at 5 years were 76% (±6%) and 68% (±6%),

respectively (Fig 1).

Cosmesis was rated by the physician as good to excel¬ lent in 89% of patients, while a fair result was present in 4%. A poor result was recorded in 7% of patients. Patients assessed their results as being good to excellent 94% of the time (Fig 2). COMMENT Radical or modified radical mastectomy has been the standard treatment for tumors 4 cm or larger in patients with breast cancer. Several studies report that the localregional recurrence rate after mastectomy alone was 20% to 32% for operable T3 tumors.15"18 Postmastectomy radia¬ tion has been performed to decrease the local-regional re¬ currence rate to approximately 15% in this setting.1921 Experience with conservative surgery and radiation for larger tumors is very limited, although some data do ex¬ ist. Toonkel et al19 reported a 12% crude local-regional re¬ currence rate in 34 patients with operable T3 breast cancer. Similarly, a study by Sheldon et al22 reported a 16% localregional recurrence rate at 5 years in 54 patients with op¬ erable T3 breast cancer treated with excisional biopsy and radiotherapy. Our study reported an actuarial localregional recurrence rate of 8.5%. Among the local-regional recurrences in our series, four of five had developed by 38 months. Other studies report that most recurrences in the breast occur within 5 years of treatment.2-5'7'23,24 Recht et al7 reported that the hazard rate for local failure after conservation management was fairly constant at approximately 2.5% per year from 2 to 6 years and then 1% per year after 8 years. In our series, three local recurrences occurred where there were positive margins of resection. Data exist in the literature to support the concept that higher local recur¬ rence rates are found in patients with positive margins of resection.1011-25 In the data reported by Kurtz et al,25 there was a 24% local recurrence rate in patients with positive microscopic margins of resection vs an 8% local recurrence rate in those with negative margins of resection. In the study by Ryoo et al,10 there was a similar conclusion, but it was noted that if a radiation boost was given to patients with positive margins, there was no significant difference in local recurrence between positive and negative margins of resection. This observation has also been supported by Solin et al.26 In our study, no patient with tumor-free mar¬ gins of resection developed a local recurrence. All patients with positive margins of resection received a radiation boost. We found no increased risk of local-regional recurrence in patients with involved axillary lymph nodes. Four of five local-regional recurrences developed in patients with negative lymph nodes. The lack of correlation between local-regional recurrence and lymph node involvement has been supported by other studies in the literature.1,5·6 Several studies have suggested a decrease in local recur¬ rence rate associated with the use of adjuvant chemother-

apy. The National

trial, using recurrence

Surgical Adjuvant Breast Project

B-06

tumors of less than 4 cm, reported a 6% local rate in patients with involved axillary lymph

nodes receiving adjuvant chemotherapy vs a 12% local re¬ currence rate in patients without axillary lymph node in¬ volvement.1 The Joint Center for Radiation Therapy27 re¬ ported a 7% local recurrence rate in patients with Tl and T2 tumors receiving adjuvant chemotherapy vs an 11% local recurrence rate in those receiving no adjuvant chemother¬ apy. In our study, there was a 5% local recurrence rate among those patients who received adjuvant chemother¬ apy vs a 7% local recurrence rate in those who did not. Cosmesis does not appear to suffer when patients with larger tumors undergo conservation management. Cos¬ mesis was rated good to excellent in 89% of our patients by physician report and 94% by patient report. This is comparable to results gathered at the University of Penn¬ sylvania, Philadelphia, where Tl and T2 tumors had a good to excellent result in 91% of patients at 5 years.6 Bea¬ dle et al28 reported good to excellent cosmetic results in 86% of patients with stage I and II breast cancer treated with conservation management. The study also reported that the size of the primary tumor (Tl or T2) did not signifi¬ cantly influence the overall cosmetic result. The relationship between tumor size and outcome has been known for many years.11-29 In 1989, Carter et al30 pub¬ lished a series of 24 740 breast cancer cases and reported that as tumor size increased, survival decreased regardless of lymph node status. Studies of patients with T3 tumors who have undergone mastectomy reveal that 5-year sur¬ vival rates range from 70% to 85% for patients with NO nodes, while it is approximately 50% for patients with Nl nodes.31-32 The results of this study compare favorably with the overall 5-year survival rate of 76% for patients with NO and Nl nodes. Breast conservation management of larger tumors does not seem to decrease overall survival rates when retrospectively compared with results from those who have undergone mastectomy. We conclude that breast-conserving surgery and radia¬ tion therapy can be effective treatment for patients with breast cancer with tumors 4 cm or larger. Overall survival, disease-free survival, and local-regional recurrence rates are acceptable and comparable with rates in series of pa¬ tients treated with more radical surgery. Cosmetic results were generally excellent. Patients with larger tumors in whom complete resection can be accomplished with ac¬ ceptable cosmetic result should be offered the option of breast conservation. We acknowledge Robert Parker, MD; Luu Tran, MD; and Aaron Fingerhut, MD; for their support and encouragement, and validating statistician, Jeremy M. G. Taylor, PhD, in the Department of Biostatistics and Radiation Oncology at UCLA, Los Angeles, Calif.

References B, Redmond C, Poisson R, et al. Eight-year results of randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med. 1989;320:822-828. 2. Sarrazin D, Le MG, Fontaine MF, Arriagada R. Conservative treatment versus mastectomy in T1 or small T2 breast cancer: a randomized clinical trial. In: Harris J, Hellman S, Silen W, eds. Conservative Management of Breast Cancer. Philadelphia, Pa: JB Lippincott; 1983:101-111. 3. Veronesi U, Saccozzi R, Del Vecchio M, et al. Comparing radical mas1. Fisher

tectomy with quadrantectomy, axillary dissection and radiotherapy

in

with small cancers of the breast. N Engl J Med. 1981 ;305:6-11. 4. Glatstein E, Strause K, Lichter A, et al. Results of the NCI early breast cancer trial. In: Proceedings of the National Institutes of Health Consensus Development Conference on Early Stage Breast Cancer; June 18-21, 1990; Bethesda, Md.

patients

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5. Clarke D, Le M, Sarrazin D, et al. Analysis of local-regional relapse in patients with early breast cancer treated by excision and radiotherapy: experience of the Institut Gustave-Roussy. Int J Radiat Oncol Biol Phys. 1985;11:

137-145. 6. Fowble B, Solin L, Schultz D, Goodman R. Ten year results of conservative surgery and irradiation for stage I and II breast cancer. Int J Radiat On-

col Biol Phys. 1991;21:269-277. 7. Recht A, Silen W, Schnitt S, et al. Time-course of local recurrence following conservative surgery and radiotherapy for early stage breast cancer. Int J Radiat Oncol Biol Phys. 1988;15:255-261. 8. Fourquet A, Campana D, Zafrani B, et al. Prognostic factors of breast recurrence in the conservative management of early breast cancer: a 25-year follow-up. Int J Radiat Oncol Biol Phys. 1989;17:719-725. 9. Bartelink H, Borger J, Van Dongen J, Peterse J. The impact of tumor size and histology on local control after breast conserving therapy. Radiother Oncol. 1988;11:297-303. 10. Ryoo M, Kagan R, Wollin M, et al. Prognostic factors for recurrence and cosmesis in 393 patients with early mammary carcinoma. Radiology.

1989;172:555-559. 11. Zafrani B, Vielh P, Fourquet A,

breast

cancer:

pathological

prognostic

et al. Conservative treatment of early value of the ductal in situ component and other local control and survival. Eur J Cancer Clin On-

variables on col. 1989;25:1645-1650. 12. Locker A, Ellis O, Morgan D, et al. Factors influencing local recurrence after excision and radiotherapy for primary breast cancer. Br J Surg. 1989;76:890-894. 13. National Institutes of Health Consensus Conference. Treatment of early stage breast cancer. JAMA. 1991;265:391-395. 14. Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457-481. 15. Rosenman J, Bernard S, Kober C, et al. Local recurrences in patients with breast cancer at the North Carolina Memorial Hospital (1970-1982). Cancer. 1986;57:1421-1425. 16. Donegan WL. Staging and primary treatment. In: Donegan WL, Spratt JS, eds. Cancer of the Breast. Philadelphia, Pa: WB Saunders Co; 1988:336-402. 17. Dao T, Nemoto T. The clinical significance of skin recurrence after radical mastectomy in women with cancer of the breast. Surg Gynecol Obstet. 1963;117:447-453. 18. Maddox W, Carpenter J, Laws H, et al. A randomized prospective trial of radical (Halsted) mastectomy versus modified radical mastectomy in 311 breast cancer patients. Ann Surg. 1983;198:207-212. 19. Toonkel L, Fix I, Jacobson L, Bamberg N, Wallach C. Locally advanced breast carcinoma: results with combined regional therapy. Int J Radiat Oncol Biol Phys. 1986;12:1583-1587. 20. Bedwinek J, Rao V, Perez C, Lee J, Fineberg B. Stage III and localized stage IV breast cancer: irradiation alone vs irradiation plus surgery. Int Radiat Oncol Biol Phys. 1982;8:31-36. 21. Brown G, Horiot J, Fletcher C, White E, Ange D. Simple mastectomy and radiation therapy for locally advanced breast cancers technically suitable for radical mastectomy. AJR Am J Roentgenol. 1974;120:67-73. 22. Sheldon T, Hayes C, Cady B, et al. Primary radiation therapy for locally advanced breast cancer. Cancer. 1987;60:1219-1225. 23. Fowble B, Solin L, Schultz M, Rubenstein J, Goodman R. Breast recurrence following conservative surgery and radiation: patterns of failure, prognosis, and pathologic findings from mastectomy specimens with implication for treatment. Int J Radiat Oncol Biol Phys. 1990;19:833-842. 24. Montague ED. Conservation surgery and radiation therapy in treatment of operable breast cancer. Cancer. 1984;53:700-704. 25. Kurts J, Jacquemier J, Amalric R, et al. Why are local recurrences after breast conserving therapy more frequent in younger patients? J Clin Oncol. 1990;8:591-598. 26. Solin L, Fowble B, Schultz D, Goodman R. The significance of the pathology margins of the tumor excision on the outcome of patients treated with definitive irradiation for early stage breast cancer. Int J Radiat Oncol Biol Phys. 1991;21:279-287. 27. Boyages J, Recht A, Connolly J, et al. Early breast cancer: predictors of breast recurrence for patients treated with conservative surgery and radiation therapy. Radiother Oncol. 1990;19:29-41. 28. Beadle G, Harris J, Silver B, et al. Cosmetic results following primary radiation therapy for early breast cancer. Cancer. 1984;54:2911-2918. 29. Fisher B, Slack N, Bross I, et al. Cancer of the breast: size of neoplasm and prognosis. Cancer. 1969;24:1071-1080. 30. Carter C, Allen C, Henson D. Relation of tumor size, lymph node status and survival in 24,740 breast cancer cases. Cancer. 1989;63:181-187. 31. Lacour J, Bucalossi E, Cacers G, et al. Radical mastectomy versus radical mastectomy plus internal mammary dissection. Cancer. 1976;37:206-214. 32. Schottenfeld D, Nash A, Robbins G, Beattie E. Ten-year results of the treatment of primary operable breast carcinoma. Cancer. 1976;38:1001\x=req-\ J

1007.

Discussion Theodore X. O'Connell, MD, Los Angeles, Calif: When con¬ servative management of breast cancer treated by partial mastec¬ tomy and radiation therapy was first introduced, certain rigid

criteria were set up to select patients. These criteria were directed at selecting patients with a low risk of both local recurrence and systemic spread. However, these criteria (though logical) were only presumed to be correct but were not fully tested in the clin¬ ical arena. As our experience with treating patients with breast cancer conservatively has increased, some of the selective criteria have been called into question and need to be vigorously tested to determine whether they are truly valid. One of these criteria is that size of the tumor is important and that tumors in the early series (only less than 2 cm) and in later series (less than 4 cm) should be treated conservatively.

There have been several reports

comparing differences of pa¬

tients with recurrences after conservative treatment with those in whom the disease did not recur. At our institution, we have done such a study to analyze several of these factors and thus to test the methods of selection. In our study as well as others, the size of the primary tumor seems to have no relation to local recurrence. However, the presence of lymph node métastases predicted a slight increase in local recurrence, but this is also associated with the presence of metastatic disease and may indicate a higher chance of overall failure, both local and systemic. From our expe¬ rience, I agree with the authors' conclusion that size does not make a tremendous impact on local recurrence. However, in our study, almost all of the patients have lesions only up to 7 cm in size, and all did well. I do not think that a sweeping statement should be made from this data presented today that size has ab¬ solutely no effect on recurrence, because in this data presented, tumors less than 6 cm had a 6% local recurrence, while those 6 or 7 cm in size had a 10% recurrence, and those over 7 cm in size failed 20%. The size may not be a factor in tumors up to 7 cm in diameter, but it may have an impact in lesions that are larger. Therefore, the selective criteria should be changed from tumors under 4 cm to those under 6 or 7 cm in size. But this report does not fully support treating tumors larger than 7 cm conservatively. Regarding cosmesis, the methods of treatment developed with the original protocols have enabled us to maintain adequate cos¬ mesis even when dealing with large tumors. These methods in¬ clude not closing the dead space, not draining the surgical cavity, and minimal removal of skin and subcutaneous tissue over the lesion. The operative site is then allowed to fill with the seroma, maintaining an adequate size and shape of the breast. In the study of our patients, we found that although cosmesis was generally excellent, the patients with the poorest cosmesis were those with large pendulous breasts with a high fat content who had signif¬ icant radiation fat necrosis. I would ask the authors whether this was also their finding in their series. It is uncommon to have local recurrence within the first 2 years after treatment, and it is has been noted in a number of reports that local recurrence can become manifest late with local recur¬ rence often doubling between 5 and 10 years. Since the range of follow-up in these patients is 4 to 132 months with a mean of 4 years, I would ask the authors to comment on how many of these 68 patients were followed for less than 2 years in which local re¬ currence would not be expected, and what is the actual percent¬ age of local recurrence in those patients who are actually followed for at least 5 years. This may give us a better idea of whether these findings of the study are valid long-term. Although this report successfully challenges one of the selective criteria of the original protocols, it seems to validate another cri¬ terion. That criterion is that positive margins should not be acceptable in the conservative treatment of patients. In the review of our patients, we found only one element that was significantly associated with local recurrence, and that was the presence of multifocal intraductal or invasive ductal disease. Interestingly, we reported this presence of multifocal disease as presumed fail¬ ure of radiation therapy to sterilize the remaining areas in the breast. However, the radiation therapy department in our insti¬ tution, reviewing the same patients, reported this not as multifo¬ cal disease but rather as patients with positive surgical margins since usually the multifocal disease was at or close to the margins of resection. It is a little bit like is the glass half full or is the glass half empty, and what specialty do you come from? You tend to

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blame the other specialty for the failure. However, they termed this to be surgical failure rather than radiation failure. I have two questions regarding the element of positive margins. First, there seems to be a large number of patients with positive margins who are not treated with mastectomy or further resec¬ tion. Why is this the case since past and current recommendations would be not to treat such patients conservatively? Second, are the positive margins that you speak of true positive margins of the tumor growing to the margin or really evidence of multifocal disease that happens to be present at or near the margin? James E. Goodnight Jr, MD, Sacramento, Calif: As we go through this evolution in the primary treatment of breast cancer, it is important that results like these be documented. The very high standard set by this paper will clearly represent a challenge to me as I conduct my practice. However, these 68 patients from four large groups represent considerable selection, and so I would echo the same question that Dr O'Connell raised. What are the selection factors? What caused the radiation oncologist or the pa¬ tient or the surgeon to choose this method of treatment for these patients with large tumors? And, in your mind, what are contraindications to breast-conserving therapy in these patients with tumors larger than 4 cm? If the lumpectomy indeed produces tumor-free margins, do you feel that a radiation boost to that site is actually necessary, and if you choose the iridium implant vs external beam boost, is there any difference in cosmesis? Dr O'Connell alluded to the "positive margins" as reviewed by the radiation oncologist or multifocal disease as reviewed by the surgeons. I might add to that, if you find extensive ductal carcinoma in situ, does that influence your choice of therapy? Finally, in the newer age of neoadjuvant chemotherapy, do you see that as the opportunity to bring more of these patients with larger tumors to breast-conserving therapy by giving preopera¬ tive chemotherapy? H. Stephens Moseley, MD, Portland, Ore: An 8.5% overall lo¬ cal recurrence rate is remarkable. It is also important to note that there have been other series that have shown recurrence rates closer to 15%. In selecting patients for local excision, the principle of an en bloc excision was glossed over by the authors. It does not matter whether the en bloc excision results in a modified radical or radical mastectomy or lumpectomy. The importance of tumorfree margins cannot be overemphasized. The authors also com¬ mented on that and had no local recurrences in the groups with tumor-free margins. I would like to ask the authors how they mark these margins. Do you do it from the lumpectomy, or do you reexcise all parts of the cavity? I would also ask that since many of the patients did receive adjuvant chemotherapy, did any of these people receive their chemotherapy prior to their lumpectomy? And finally, an observation about breast conservation: cosme¬ sis is the name of the game. For those of us that occasionally watch television or the movies, I think that women in Los Angeles may have more ample breasts than those at least in Portland. For many of the women, a greater than 4-cm lumpectomy would essentially constitute a modified radical mastectomy. JOSEPH A. IGNATIUS, MD, San Francisco, Calif: I wanted to make a couple of observations about the importance being given to socalled tumor-free margins by both the primary author and the discussants. There have been two recent studies that have shown poor correlation between the initial evaluation of the excision specimen margins and what has been found in the excision bed in those patients who have gone on to mastectomy, including margins that have been read as tumor-free by the pathologist and residual invasive cancer has been found in the mastectomy spec¬ imen, and margins that have been read as involved and no resid¬ ual invasive cancer is found. So I would caution you against placing too great a reliance on the accuracy of margin involve¬ ment as reported by the pathologist. It is also worth noting that many centers in the United States and abroad that are employing conservation management do not place emphasis on the necessity of achieving microscopic tumor-free margins, despite the original recommendations of the NSABP trials mandating tumor-free

for conservation treatment; so this whole issue may have limited practical significance. LAWRENCE A. DANTO, MD, Davis, Calif: The major thrust for breast conservation therapy has been the premise that women will have a better life-style and emotional state of well-being if their breasts can be conserved when treated for carcinoma of the breast. But the question still remains to be answered: Do these women in fact have a better life-style and emotional state of wellbeing? A recent study in the New England journal of Medicine sug¬ gests that this may, in fact, not be the case. I wonder if the authors have compared their breast conservation group to their mastec¬ tomy group with respect to life-style and state of well-being? EDWARD V. Snyder Jr, MD, Pasadena, Calif: I would like to take umbrage with some of the things Dr Hanna has said. You will re¬ member that on the slide presented concerning the article from Surgical Clinics of North America, one of the relative factors involved in the treatment of breast cancer was size of the patient's breast. In this paper, there is no mention of this. If you will all look at these little cards in front of you, you will notice the embossed flower. It measures 4 cm in cross-sectional diameter. Remember that if we are talking about a tumor mass that is 4 cm, we are talking 4 cm in all diameters. If you go out 1 cm on all sides to obtain an adequate tumor margin, that then makes a mass of tissue 6 cm in all directions. That is just about the size of the bottom of this glass in front of you. The open side of the glass is 8 cm in diameter. If the surgeon is to remove a 6 to 8-cm mass of tissue or greater from a lady with an A or cup breast size, all or almost all of the breast will be excised. As a result, an acceptable cosmetic repair is impossible to achieve. Since 20% to 40% of women are in this category, only those patients with large breasts qualify for conservative treat¬ ment while achieving acceptable cosmesis if they have a breast cancer greater than 4 cm. Now the lady that sells expensive swimwear tells me that in the islands, approximately 20% of the bra sizes are an A cup. Of course, that is probably influenced by the number of Orientals. She says that probably another 20% to 40% of the women will be a cup. Now remember, we are talk¬ ing 6-cm tumors to 14-cm tumors removed from patients with breasts this size. You will notice the slides that the young lady presented. That one was probably a D patient, and the other pa¬ tient was probably a double D or an E. Therefore, I think that to their selection factors, the authors should add the size of the pa¬ tients' breast at the start of the procedure. RICHARD P. Saik, MD, San Diego, Calif: Can you elucidate the status of those with positive margins? At the Scripp's Clinic we have been reresecting women or offering mastectomy in those that have an invasive positive margin and not radiating those women. However, in those that have one positive focal area of the in situ carcinoma, our radiation therapists have been willing to treat these women even though I must admit myself I am a little nervous about the outcome of that. I did not see in your results what the breakdown in the group with positive margins was. Are these all invasive positive margins or just in situ positive margins? How many of the margins are positive when you say positive? How do you treat those with in situ positive margins? For these large masses, we usually proceed with mastectomy unless there is only in situ carcinoma in the margin. I agree with resection and breast preservation as you have pre¬ sented, but these patients must be prepared to have further sur¬ gery if necessary. DR GIULIANO: First, I agree with many of the discussants who commented on breast size and tumor size. While I personally have not performed the epidemiologie studies on breast size as did one discussant, it is quite clear that a 4-cm tumor in a small breast is a lot harder to deal with and achieve acceptable cosmesis than a 6-cm tumor in a very large breast. The importance of size is prob¬ ably the ratio of breast to tumor volume rather than the absolute size of the tumor. That is what prompted this study. There is nothing magic about 4 cm. Why would anyone pick 4 cm as a boundary? Dr O'Connell, in his discussion, said that we should reconsider, and perhaps a new upper limit of resection should be 7 cm. I maintain that 7 cm is not a magic boundary either. It is the

margins as a requisite

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size of the breast and the size of the tumor that will permit breast conservation in experienced hands. A number of discussants, including Dr O'Connell, initially com¬ mented on the large number of positive margins and the multiple groups of contributing physicians. There were really only two groups. However, the patients in this study were identified through the computerized files of the two groups of radiothera¬ pists, so we really have a number of different surgeons and sur¬ geons of different experience. The margins were truly positive margins with infiltrating cancer and not merely in situ disease. In my practice, I always reexcise the biopsy site, and I personally ori¬ ent the specimen and margins with multiple sutures and usually show it to the pathologist and orient it for him in person. I think on a second reexcision with a well-oriented specimen, the negative margin is more likely to be truly negative. We believe, as this study showed, that margins are very important prognostically in deter¬ mining local recurrence. Margins are probably the single best prognostic parameter in the literature and in our experience as well. I always perform a second reexcision even if I did the initial biopsy myself and thought the margins were negative. Of course, this is a highly select group of patients. Initially, there were patients who refused mastectomy. Then there were patients who were operated on because of surgeon bias. It just did not make sense to me personally to have a patient with a very large breast with a 5-cm tumor be told that she must have a mastec¬ tomy. So the discussants are correct; of course there is bias, but the important thing is that size alone is not a contraindication to breast conservation. Dr Goodnight asked if we saw any difference in cosmesis when comparing different forms of radiotherapy, external beam, and iridium. No, we did not see differences in cosmesis. I personally see no need for iridium implants in most patients. None of these

received neoadjuvant chemotherapy. Bonnadonna has advocated preoperative chemotherapy for tumors greater than 3 cm to diminish their size in order to make them resectable for breast conservation. We did not do that in these patients. We do use neoadjuvant chemotherapy, however, for different reasons in some patients not included in this study. Dr Danto raised the interesting question: Is this all worth it? Why do this? Are these patients happier? There is no question in my mind that these patients are happier, especially if they orig¬ inally request conservation. In addition, the NIH Consensus Conference took into consideration the psychological well-being of patients. It is quite clear if you ask women you know—all things being equal—would you rather have your breast or lose your breast? The answer is quite obvious! Most women would prefer to keep their breasts when overall survival is equivalent to

patients

mastectomy.

Despite the size of the flower on your coaster carefully measured by Dr Snyder, one of our members, we feel that breast conservation is appropriate for tumors that are greater than 4 cm. We began this review because it seemed apparent that there is nothing magic about 4 cm. Larger tumors in large breasts may be better treated with conservation than smaller tumors in small breasts. Regardless of tumor size, the operation should be conducted by removing the tumor or prior biopsy site by transecting only normal-appearing fat or parenchyma. Abnormal-appearing areas should be examined with intraopera¬ tive frozen sections. The fundamental principle is complete tumor resection with an adequate rim of normal tissue resulting in tumor-free margins and an acceptable cosmetic result. It is clear to me that with proper judgment and technique, breastconserving treatment is appropriate for women with tumors of any size.

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