Originally published as JCO Early Release 10.1200/JCO.2005.02.7888 on April 24 2006

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Ten-Year Multi-Institutional Results of Breast-Conserving Surgery and Radiotherapy in BRCA1/2-Associated Stage I/II Breast Cancer

Lori J. Pierce, Albert M. Levin, Timothy R. Rebbeck, Merav A. Ben-David, Eitan Friedman, Lawrence J. Solin, Eleanor E. Harris, David K. Gaffney, Bruce G. Haffty, Laura A. Dawson, Steven A. Narod, Ivo A. Olivotto, Andrea Eisen, Timothy J. Whelan, Olufunmilayo I. Olopade, Claudine Isaacs, Sofia D. Merajver, Julia S. Wong, Judy E. Garber, Barbara L. Weber

From the University of Michigan School of Medicine; University of Michigan School of Public Health, Ann Arbor, MI; Center for Clinical Epidemiology and Biostatistics and Abramson Family Cancer Research Institute, University of Pennsylvania; University of Pennsylvania School of Medicine, Philadelphia, PA; University of Utah School of Medicine, Salt Lake City, UT; UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ; Lombardi Cancer Center, Georgetown University, Washington, DC; Dana-Farber Cancer Institute, Harvard University, Boston, MA; University of Chicago School of Medicine, Chicago, IL; Princess Margaret Hospital, University of Toronto, Toronto; Hamilton Regional Cancer Center, Hamilton, Ontario; British Columbia Cancer Agency, Victoria, BC, Canada; and Sheba Medical Center, Ramat Gan, Israel

Address reprint requests to and reprint requests to Lori J. Pierce, MD, Department of Radiation Oncology, University of Michigan School of Medicine, 4308 Cancer and Geriatrics Center, 1500 E Medical Center Dr, Ann Arbor, MI 48109-0010; e-mail: ljpierce{at}umich.edu

PURPOSE: We compared the outcome of breast-conserving surgery and radiotherapy in BRCA1/2 mutation carriers with breast cancer versus that of matched sporadic controls.

METHODS: A total of 160 BRCA1/2 mutation carriers with breast cancer were matched with 445 controls with sporadic breast cancer. Primary end points were rates of in-breast tumor recurrence (IBTR) and contralateral breast cancers (CBCs). Median follow-up was 7.9 years for mutation carriers and 6.7 years for controls.

RESULTS: There was no significant difference in IBTR overall between carriers and controls; 10- and 15-year estimates were 12% and 24% for carriers and 9% and 17% for controls, respectively (hazard ratio [HR], 1.37; P = .19). Multivariate analyses for IBTR found BRCA1/2 mutation status to be an independent predictor of IBTR when carriers who had undergone oophorectomy were removed from analysis (HR, 1.99; P = .04); the incidence of IBTR in carriers who had undergone oophorectomy was not significantly different from that in sporadic controls (P = .37). CBCs were significantly greater in carriers versus controls, with 10- and 15-year estimates of 26% and 39% for carriers and 3% and 7% for controls, respectively (HR, 10.43; P < .0001). Tamoxifen use significantly reduced risk of CBCs in mutation carriers (HR, 0.31; P = .05).

CONCLUSION: IBTR risk at 10 years is similar in BRCA1/2 carriers treated with breast conservation surgery who undergo oophorectomy versus sporadic controls. As expected, CBCs are significantly increased in carriers. Although the incidence of CBCs was significantly reduced in mutation carriers who received tamoxifen, this rate remained significantly greater than in controls. Additional strategies are needed to reduce contralateral cancers in these high-risk women.

Supported by grants from The Breast Cancer Research Foundation (to L.J.P. and B.L.W.), National Institutes of Health Grant No. M01 RR00064 (to D.K.G.), and National Cancer Institute Grant No. P30 CA51008-12 (to C.I.).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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