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Originally published as JCO Early Release 10.1200/JCO.2002.11.101 on July 22 2002 © 2002 American Society for Clinical Oncology Tamoxifen, Radiation Therapy, or Both for Prevention of Ipsilateral Breast Tumor Recurrence After Lumpectomy in Women With Invasive Breast Cancers of One Centimeter or LessByFrom the National Surgical Adjuvant Breast and Bowel Project Biostatistical Center, Division of Pathology, and Breast Committee; The University of Pittsburgh; and Allegheny General Hospital, Pittsburgh, PA; Department of Health Studies, The University of Chicago, Chicago, IL; Cancer Center, Aultman Hospital, Canton, OH; Jewish General Hospital, Montreal, Canada; and Division of Radiation Oncology, Mayo Clinic, Rochester, MN. This article was published ahead of print at www.jco.org.Address reprint requests to Bernard Fisher, MD, NSABP, 4 Allegheny Center, Suite 602, Pittsburgh, PA, 15212-5234; email: bernard.fisher{at}nsabp.org
PURPOSE: This trial was prompted by uncertainty about the need for breast irradiation after lumpectomy in node-negative women with invasive breast cancers of  1 cm, by speculation that tamoxifen (TAM) might be as or more effective than radiation therapy (XRT) in reducing the rate of ipsilateral breast tumor recurrence (IBTR) in such women, and by the thesis that both modalities might be more effective than either alone. PATIENTS AND METHODS: After lumpectomy, 1,009 women were randomly assigned to TAM (n = 336), XRT and placebo (n = 336), or XRT and TAM (n = 337). Rates of IBTR, distant recurrence, and contralateral breast cancer (CBC) were among the end points for analysis. Cumulative incidence of IBTR and of CBC was computed accounting for competing risks. Results with two-sided P values of .05 or less were statistically significant. RESULTS: XRT and placebo resulted in a 49% lower hazard rate of IBTR than did TAM alone; XRT and TAM resulted in a 63% lower rate than did XRT and placebo. When compared with TAM alone, XRT plus TAM resulted in an 81% reduction in hazard rate of IBTR. Cumulative incidence of IBTR through 8 years was 16.5% with TAM, 9.3% with XRT and placebo, and 2.8% with XRT and TAM. XRT reduced IBTR below the level achieved with TAM alone, regardless of estrogen receptor (ER) status. Distant treatment failures were infrequent and not significantly different among the groups (P = .28). When TAM-treated women were compared with those who received XRT and placebo, there was a significant reduction in CBC (hazard ratio, 0.45; 95% confidence interval, 0.21 to 0.95; P = .039). Survival in the three groups was 93%, 94%, and 93%, respectively (P = .93).
CONCLUSION: In women with tumors
THREE EVENTS OCCURRED during the 1980s that influenced the diagnosis and treatment of primary breast cancer. Findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-06 randomized trial established the worth of radiation therapy (XRT) in the prevention of ipsilateral breast tumor recurrence (IBTR) after lumpectomy in women with tumors that were associated with either negative or positive axillary nodes;1 the use of better mammographic screening techniques facilitated the identification of invasive breast cancers that were too small for clinical detection (occult tumors); and findings from trials demonstrated a benefit from tamoxifen (TAM) in women with estrogen receptor (ER)-positive tumors.2,3
As lumpectomy and XRT became more common, physicians and women began to question the need for breast irradiation after lumpectomy for occult, invasive cancer. It was also thought that TAM might be just as effective as XRT in reducing the rate of IBTR and, at the same time, might result in a decrease in both the recurrence rate at other sites and the occurrence of cancer in the contralateral breast. In 1989, the NSABP implemented the B-21 study, a randomized trial that had been designed to resolve those uncertainties. This report provides information obtained from that trial about whether treatment with TAM alone is as or more effective than XRT for preventing IBTR after lumpectomy for tumors of
Study Information Before they entered the trial, women at NSABP institutions in the United States and Canada who had elected to participate in the study signed a consent form that was in compliance with federal and institutional guidelines. To be eligible, women had to have a primary invasive breast tumor of less than 1 cm in its greatest diameter, as determined by pathologic examination. If a tumor had intraductal, as well as an invasive component, the maximum diameter of both, when measured together, had to be less than 1 cm. If the pathologic size of a tumor was not available, both the clinical and mammographic sizes of the tumor had to be less than 1 cm. In addition, all tumors had to have been removed by lumpectomy and axillary dissection, margins of the resected specimen had to be tumor-free on pathologic examination, and axillary lymph nodes had to be negative on histologic examination.
The trial was opened to enrollment on June 1, 1989. After stratification by age, ie,
Patient Characteristics The distribution of selected patient and tumor characteristics was similar among the three groups (Table 2). Approximately 80% of the women were aged  50 years. Between 26% and 29% of tumors were T1a ( 5 mm) and 70% to 72% were T1b (5.1 to 10 mm). Approximately 6% to 7% of the tumors were 1 cm in size.
Therapy The techniques of lumpectomy, axillary dissection, pathologic determination of resected specimen margin status, and XRT have been described elsewhere.4 XRT was usually begun approximately 14 days after surgery, and 50 Gy was administered over a 5-week period. External-beam boosts were not assigned by randomization but were left to the discretion of the investigator. Approximately 25% of the women received a boost; around 75% did not. The median boost dose among those who received a boost was 10 Gy. Any findings that might have resulted from a comparison between women who received a boost and those who did not could have been a result of patient selection bias. Thus, because these results would have been difficult to interpret, they have not been included in this report. TAM or placebo (10 mg tablets bid) was begun within 35 days after lumpectomy and was to be given twice a day for 5 years. Because the placebo and TAM tablets could not be distinguished from each other, neither medical personnel nor patients could determine with certainty which of the pills were being administered. Five percent of women discontinued TAM or placebo because of toxicity, and 11% withdrew for other reasons.
Determination of ER
Statistical Methods Other end points that were compared across treatments included disease-free survival, time to first distant failure, time to CBC, and overall survival. Events used in the determination of disease-free survival included IBTRs, other recurrences, CBC, other second primary cancers, and deaths before treatment failure or second primary cancer. Deaths from all causes were included in the analysis of overall survival. Analyses followed the intent-to-treat principle and so were based on all 1,000 women with follow-up, including two patients who had positive specimen margins. The analyses reflect information received at the NSABP Biostatistical Center through December 31, 2000. The median time on study was 86.9 months.
Type and Location of First Events Since study entry, 187 (18.7%) of the women have had an event, ie, a tumor recurrence, CBC, other second primary cancer, or death with no evidence of cancer. Nearly two thirds of the first events (n = 120; 64.2%) were breast cancer-related: 77 were IBTRs; 16 were recurrences at other local, regional, or distant sites; and 27 were CBCs (Table 3). Forty-six first events were second primary cancers other than CBC, and 21 first events were deaths unrelated to either breast cancer recurrence or second primary cancer.
Frequency of IBTR When the hazard rates of IBTR among all women were compared, XRT and placebo resulted in a 49% lower hazard rate than treatment with TAM alone (Table 4). Treatment with XRT and TAM resulted in a 63% reduction in the rate of IBTR when compared with XRT and placebo, and an 81% reduction when compared with TAM alone. Through 8 years, the cumulative incidence of IBTR was 16.5% in TAM-treated women, 9.3% in women who received XRT and placebo, and 2.8% in those treated with XRT and TAM (Fig 1).
IBTRs According to Pathologic Type or to Age of Women at Randomization Reports from institutional pathologists were available for 76 of 77 IBTRs. Fifty-nine (77.6%) of these were invasive cancer, and 17 (22.4%) were noninvasive cancer, ie, ductal carcinoma-in-situ (DCIS). Thirty-nine (11.7%) of the women in the TAM-treated group had an invasive IBTR, and five (1.5%) had a noninvasive IBTR. There were 14 invasive IBTRs (4.2%) and nine noninvasive IBTRs (2.7%) in the XRT and placebo group. Six women (1.8%) in the XRT and TAM group had invasive IBTRs, and three (0.9%) had noninvasive IBTRs. Pathology reports describing the primary invasive tumors in the 17 women who subsequently developed noninvasive IBTRs showed an extensive DCIS component associated with the invasive cancer in 13.
In women aged
Treatment of IBTR
Time to Distant Treatment Failure
CBC
Relation of Tumor ER Status to IBTR and to CBC In women with either ER-negative or ER-positive tumors, the rate of IBTR in the XRT and placebo group was lower than the rate in the TAM-treated group (Table 4). When the XRT and TAM group was compared with the group that received XRT and placebo, there was no significant reduction in the rate of IBTR in women with ER-negative tumors. Women with ER-positive tumors who received XRT and TAM had a nonsignificantly lower rate of IBTR than those who received XRT and placebo. However, a significant reduction in the rate of IBTR was observed with XRT and TAM when that group was compared with the TAM-treated group, regardless of ER status. Tests of a differential benefit from treatment according to ER status did not reveal a statistically significant variation in the relative benefit of the combined treatments over the benefits achieved with TAM alone or with XRT and placebo. However, the number of IBTRs was insufficient to provide adequate power for such tests of interaction. In women with ER-positive tumors, the rate of occurrence of CBC was significantly less in those who received TAM, either with or without XRT, when this rate was compared with that in the XRT and placebo group (HR, 0.26; 95% CI, 0.09 to 0.78; P = .013). There were too few events in either group of women with ER-negative tumors to permit obtaining meaningful findings.
Size of Primary Tumor and Size as a Prognostic Factor for IBTR
Comparison Between Size of Tissue Specimens and Size of Primary Tumor Removed by Lumpectomy in Women With IBTR
Survival
Adverse Events Hot flashes were more frequent in TAM-treated women than in those who received placebo. Nine (1.4%) of the women who received TAM, with or without XRT, had deep vein thrombosis (DVT); five (0.8%) had nonfatal pulmonary embolism (PE); and five (0.8%) had stroke. No DVTs were reported among women in the XRT and placebo group; one patient (0.3%) in this group had PE, and two (0.6%) had stroke. Ten (67%) of the DVTs or PEs in the 15 women who experienced either of those events and five (71%) of the seven strokes occurred in women who were older than 65 years of age at the time of study entry.
After we demonstrated that XRT resulted in a decrease in the rate of IBTR after lumpectomy,1 there was speculation about whether the incidence of IBTR in women with invasive tumors of 1 cm might be low enough to spare them the need for breast irradiation. At that time, no information was available about the frequency of IBTR after removal of such small tumors. Only after the B-21 study was already in progress were there reports of such findings from randomized2,7-13 and retrospective studies.14-16 Seventy-two of 572 participants in the NSABP B-06 trial who had tumors of 1 cm were treated with lumpectomy alone; 25% of these women had an IBTR through 8 years of follow-up.17 In another randomized trial in which 93 women with tumors of 1 cm had been treated with lumpectomy, 22.5% had a local recurrence through 10 years of follow-up.9 In a nonrandomized study, a similar frequency of IBTR (24% at 10 years) was found in women with tumors of 1 cm who had been treated with lumpectomy.14 Although the frequency of an IBTR after lumpectomy in approximately 25% of women might be viewed as being too high for such small tumors, the plausibility of that frequency is supported by the findings in our current report, which demonstrate indirectly that there is likely to be a substantial risk of an IBTR after lumpectomy to remove tumors of 1 cm. There is ample reason to believe that the cumulative incidence of IBTR (17% through 8 years of follow-up) in the TAM-treated group in B-21 would have been higher in an untreated control group, had such a group been included in that study. This thesis is supported by the finding that 82% of the tumors in women in the TAM-treated group in B-21 were ER positive, and it has repeatedly been demonstrated that TAM benefits women with all stages of ER-positive invasive breast cancer2,18-22; prevents ER-positive invasive cancer in women at increased risk for invasive cancer,23 including those with a history of DCIS,13 lobular carcinoma-in-situ, and atypical ductal hyperplasia23; and prevents CBC.24-26 Thus, there is conclusive evidence that the incidence of IBTR after removal of an invasive tumor of 1 cm is high enough to warrant evaluation of the worth of additional therapy after lumpectomy.
The B-21 findings provide information from a randomized clinical trial that was designed a priori for the specific purpose of comparing the worth of TAM and/or XRT in reducing the incidence of IBTR and CBC after lumpectomy in node-negative women with tumors of Information from studies recently published by other investigators with regard to the use of TAM and XRT in older women is relevant to our findings. In one of the studies, axillary node–negative women with T1 and T2 tumors who were over 50 years of age (median age, 68 years) were randomly assigned after lumpectomy to receive either TAM or TAM in addition to XRT.27 After a median follow-up time of 3.4 years, the investigators concluded that treatment with TAM and XRT resulted in a significantly lower rate of IBTR than did treatment with TAM alone, a conclusion that was consistent with our findings. However, the findings from a second study, in which TAM with XRT was compared with TAM alone in lumpectomy-treated women aged 70 years or older who had clinical stage I, ER-positive breast cancer, led to a different conclusion.28 After a median time on study of only 2.8 years, the authors concluded, from a few events, that XRT might not be of clinical benefit in the elderly population that was evaluated. That thesis has been promulgated by several other investigators, who have hypothesized that, in node-negative women over 60 years of age, XRT after breast-conserving surgery might not be necessary.8,15,29-32 The B-21 findings demonstrated that the rate of IBTR in women of all ages who received XRT and TAM was lower than the rate in women who received TAM alone; thus, they are not in concordance with findings that refute the use of XRT on the basis of age. Because, as we have noted in this report, many of the IBTRs that occurred in women in the B-21 study were diagnosed only after a prolonged time interval, ie, 38% after 5 years, the value of the findings as reported in the two studies previously noted is diminished by the short follow-up time in each. Some have contended that the higher-than-expected frequency of IBTR after lumpectomy for small, invasive or noninvasive breast cancer is a result of the removal of an insufficient amount of normal breast tissue surrounding a tumor.30,33,34 It has been suggested that more expansive surgical procedures would achieve better local tumor control and, thus, could preclude the need for XRT. Although the appropriate width of tumor-free breast tissue that should encompass an excised tumor has not yet been determined,35 it is generally believed that tumor-free specimen margins should be at least 10 mm. In the B-21 study, we demonstrated that the smallest diameter of the resected specimen was generally at least 10 mm greater than the largest diameter of the tumor. Thus, these findings suggest that the frequency of IBTR observed in B-21 is not likely to be due to the removal of an inadequate amount of normal tissue surrounding the tumor.
In 1998, an international consensus panel decided that the size of an invasive tumor was the most important prognostic factor for estimating the risk of relapse in women with node-negative breast cancer.36 Tumors of
Most investigators have indicated a preference for salvage mastectomy in treating women diagnosed with an IBTR.37-40 Nearly one half (44.3%) of the women in B-21 who had an IBTR were managed with a second breast-conserving operation. Because almost half of the women with an invasive IBTR who were treated with mastectomy had IBTRs that were
The B-21 findings and their implications for treatment are likely to be interpreted diversely. Such has been the case after publication of findings from other NSABP trials that have evaluated the prognosis and treatment of women with tumors of
We do not suggest that all women with invasive or noninvasive breast cancers of
APPENDIX Aultman Hospital, Canton, OH, E.P. Mamounas, MD; Baptist Regional Cancer Institute, Jacksonville, FL, N. Abramson, MD; Boston Medical Center, Boston, MA, M.T. Kavanah, MD; British Columbia Cancer Agency, Vancouver, British Columbia, Canada, L.M. Weir, MD; Community Clinical Oncology Program (CCOP), Atlanta Regional, Atlanta, GA, T.E. Seay, MD; CCOP, Columbia River Oncology Program, Portland, OR, K.S. Lanier, MD; CCOP, Kalamazoo, MI, R.S. Lord, III, MD; CCOP, Marshfield Clinic, Marshfield, WI, J.L. Hoehn, MD; CCOP, Scott and White Clinic, Temple, TX, R.R. Young, MD; CCOP, Southeast Cancer Control Consortium, Winston-Salem, NC, J.N. Atkins, MD; CCOP, The Duluth Clinic, Duluth, MN, R.J. Dalton, MD; Centre Hospitalier de l’Universite de Montreal, Montreal, Quebec, A. Robidoux, MD; Centre Hospitalier Affilie–Pavillon Saint-Sacrement, Quebec, Canada, J. Robert, MD; City of Hope National Medical Center, Duarte, CA, L.D. Wagman, MD; Cross Cancer Institute, Edmonton, Canada, A.W. Lees, MD; Jewish General Hospital, Montreal, Canada, R.G. Margolese, MD; Kent County Memorial Hospital, Warwick, RI, A. Thomas, MD; Minority-Based Community Clinical Oncology Program, VA Commonwealth University, Richmond, VA, J.D. Roberts, MD; Michigan State University, E. Lansing, MI, A.P. Scholnik, MD; Montreal General Hospital, Montreal, Canada, M.P. Thirlwell, MD; Ohio State University, Columbus, OH, W.B. Farrar, MD; Rockford Clinic, Rockford, IL, W.R. Edwards, MD; Royal Victoria Hospital, Montreal, Canada, H.R. Shibata, MD; Tom Baker Cancer Centre, Calgary, Canada, A.H.G. Paterson, MD; University of Cincinnati, Cincinnati, OH, E.A. Shaughnessy, MD; University of Hawaii, Honolulu, HI, R.H. Oishi, MD; University of Medicine/Dentistry, New Brunswick, NJ, T. Kearney, MD; University of Pittsburgh, Pittsburgh, PA, V.G. Vogel, III, MD; University of Vermont, Burlington, VT, S.P. Harlow, MD.
Supported by Public Health Service grant nos. U10-CA-12027, U10-CA-69651, U10-CA-37377, and U10-CA-69974 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD. We thank Linda Gilarski and Marlon Jones, data managers; Cheryl Butch, RN, medical reviewer; Gordon Bass for technical support; Tanya Spewock for editorial assistance; and Mary Hof for preparation of the article.
1. 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 breast cancer. N Engl J Med 312: 665-673, 1985[Abstract] 2. Fisher B, Costantino J, Redmond C, et al: A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med 320: 479-484, 1989[Abstract] 3. Early Breast Cancer Trialists’ Collaborative Group: Tamoxifen for early breast cancer: An overview of the randomised trials. Lancet 351: 1451-1467, 1998[CrossRef][Medline] 4. Fisher B, Wolmark N, Fisher ER, et al: Lumpectomy and axillary dissection for breast cancer: Surgical, pathological and radiation considerations. World J Surg 9: 692-698, 1985[CrossRef][Medline] 5. Gaynor JJ, Feuer EJ, Tan CC, et al: On the use of cause-specific failure and conditional failure probabilities: Examples from clinical oncology data. J Am Stat Assoc 88: 400-409, 1993[CrossRef] 6. Prentice RL, Kalbfleisch JD, Peterson AV, et al: The analysis of failure times in the presence of competing risks. Biometrics 34: 541-554, 1978[CrossRef][Medline]
7. Liljegren G, Holmberg L, Adami HO, et al: Sector resection with or without postoperative radiotherapy for stage I breast cancer: Five-year results of a randomized trial. J Natl Cancer Inst 86: 717-722, 1994
8. Veronesi U, Luini A, Del Vecchio M, et al: Radiotherapy after breast-preserving surgery in women with localized cancer of the breast. N Engl J Med 328: 1587-1591, 1993
9. Clark RM, Whelan T, Levine M, et al: Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: An update. J Natl Cancer Inst 88: 1659-1664, 1996 10. Forrest AP, Stewart HJ, Everington D, et al: Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Lancet 348: 708-713, 1996[CrossRef][Medline] 11. Renton SC, Gazet JC, Ford HT, et al: The importance of the resection margin in conservative surgery for breast cancer. Eur J Surg Cancer 22: 17-22, 1996 12. Stewart HJ, Prescott RJ, Forrest PA: Conservation therapy of breast cancer. Lancet 2: 168-169, 1989 (letter)[Medline] 13. Fisher B, Dignam J, Wolmark N, et al: Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet 353: 1993-2000, 1999[CrossRef][Medline] 14. McCready DR, Hanna W, Kahn H, et al: Factors associated with local breast cancer recurrence after lumpectomy alone. Ann Surg Oncol 3: 358-366, 1996[CrossRef][Medline] 15. Elkhuizen PHM, van de Vijver MJ, Hermans J, et al: Local recurrence after breast-conserving therapy for invasive breast cancer: High incidence in young patients and association with poor survival. Int J Radiat Oncol Biol Phys 40: 859-867, 1998[CrossRef][Medline] 16. Fowble B: Is there a subset of patients with early stage invasive breast cancer for whom irradiation may not be indicated after conservative surgery alone? Breast J 1: 75-90, 1995 (review) 17. Fisher B, Redmond C: Lumpectomy for breast cancer: An update of the NSABP experience. J Natl Cancer Inst Monogr 11: 7-13, 1992 18. Margreiter R, Wiegele J: Tamoxifen (Nolvadex) for premenopausal patients with advanced breast cancer. Breast Cancer Res Treat 4: 45-48, 1984[CrossRef][Medline] 19. Nolvadex Adjuvant Trial Organisation: Controlled trial of tamoxifen as single adjuvant agent in management of early breast cancer. Lancet 1: 836-840, 1985[Medline] 20. Report from the Breast Cancer Trials Committee: Scottish Cancer Trials Office (MRC). Adjuvant tamoxifen in the management of operable breast cancer: The Scottish trial. Edinburgh Lancet 2:171-175, 1987
21. Fisher B, Redmond C, Brown A, et al: Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project trial. J Clin Oncol 4: 459-471, 1986
22. Fisher B, Dignam J, Tan-Chiu E, et al: Prognosis and treatment of patients with breast tumors of one centimeter or less and negative axillary lymph nodes. J Natl Cancer Inst 93: 112-120, 2001
23. Fisher B, Costantino JP, Wickerham DL, et al: Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 90: 1371-1388, 1998
24. Rutqvist LE, Cedermark B, Glas U, et al: Contralateral primary tumors in breast cancer patients in a randomized trial of adjuvant tamoxifen therapy. J Natl Cancer Inst 83: 1299-1306, 1991 25. Cancer Research Campaign Adjuvant Breast Trial Working Party: Cyclophosphamide and tamoxifen as adjuvant therapies in the management of breast cancer. Br J Cancer 57: 604-607, 1988[Medline]
26. Fisher B, Dignam J, Bryant J, et al: Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 88: 1529-1542, 1996 27. Fyles A, McCready D, Manchul L, et al: Preliminary results of a randomized study of tamoxifen +/- breast radiation in T1/2 NO disease in women over 50 years of age. Proc Am Soc Clin Oncol 20: 24A, 2001 (abstr 92) 28. Hughes KS, Schnaper L, Berry D, et al: Comparison of lumpectomy plus tamoxifen with and without radiotherapy (RT) in women 70 years of age or older who have clinical stage I, estrogen receptor positive (ER+) breast carcinoma. Proc Am Soc Clin Oncol 20: 24A, 2001 (abstr 93)
29. Liljegren G, Lindgren A, Bergh J, et al: Risk factors for local recurrence after conservative treatment in stage I breast cancer: Definition of a subgroup not requiring radiotherapy. Ann Oncol 8: 235-241, 1997 30. Gruenberger T, Gorlitzer M, Soliman T, et al: It is possible to omit postoperative irradiation in a highly selected group of elderly breast cancer patients. Breast Cancer Res Treat 50: 37-46, 1998[CrossRef][Medline]
31. Veronesi U, Marubini E, Mariani L, et al: Radiotherapy after breast-conserving surgery in small breast carcinoma: Long-term results of a randomized trial. Ann Oncol 12: 997-1003, 2001 32. Borger J, Kemperman H, Hart A, et al: Risk factors in breast-conservation therapy. J Clin Oncol 12: 653-660, 1994[Abstract]
33. Silverstein MJ, Lagios MD, Groshen S, et al: The influence of margin width on local control of ductal carcinoma in situ of the breast. N Engl J Med 340: 1455-1461, 1999 34. Holland PA, Gandhi A, Knox WF, et al: The importance of complete excision in the prevention of local recurrence of ductal carcinoma in situ. Br J Cancer 77: 110-114, 1998[Medline] 35. Obedian E, Haffty BG: Negative margin status improves local control in conservatively managed breast cancer patients. Cancer J Sci Am 6: 28-33, 1999
36. Goldhirsch A, Glick JH, Gelber RD, et al: Meeting highlights: International Consensus Panel on the Treatment of Primary Breast Cancer. J Natl Cancer Inst 90: 1601-1608, 1998 37. Voogd AC, van Tienhoven G, Peterse HL, et al: Local recurrence after breast conservation therapy for early stage breast carcinoma: Detection, treatment, and outcome in 226 patients. Cancer 85: 437-446, 1999[CrossRef][Medline] 38. Osteen RT: Risk factors and management of local recurrence following breast conservation surgery. World J Surg 18: 76-80, 1994[CrossRef][Medline] 39. Dipaola RS, Orel SG, Fowble BL: Ipsilateral breast tumor recurrence following conservative surgery and radiation therapy. Oncology 8: 59-68, 1994 40. Francis M, Cakir B, Ung O, et al: Prognosis after breast recurrence following conservative surgery and radiotherapy in patients with node-negative breast cancer. Br J Surg 86: 1556-1562, 1999[CrossRef][Medline] 41. Fisher B, Dignam J, Wolmark N, et al: Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: Findings from National Surgical Adjuvant Breast and Bowel Project B-17. J Clin Oncol 16: 441-452, 1998[Abstract]
42. Gelber RD, Goldhirsch A: Radiotherapy to the conserved breast: Is it avoidable if the cancer is small? J Natl Cancer Inst 86: 652-654, 1994 43. Wong JS, Harris JR: Importance of local tumour control in breast cancer. Lancet Oncol 2: 11-17, 2001[CrossRef][Medline] Submitted November 20, 2001; accepted June 24, 2002.
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Copyright © 2002 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
