Risk of Asynchronous Contralateral Breast Cancer in Noncarriers of BRCA1 and BRCA2 Mutations With a Family History of Breast Cancer: A Report From the Women's Environmental Cancer and Radiation Epidemiology Study.

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Anne S. Reiner, Jennifer D. Brooks, Marinela Capanu, Xiaolin Liang, Malcolm C. Pike, Colin B. Begg, and Jonine L. Bernstein, Memorial Sloan-Kettering Cancer Center, New York, NY; Esther M. John, Cancer Prevention Institute of California, Fremont; Leslie Bernstein, Beckman Research Institute, City of Hope, Duarte; Jane C. Figueiredo, Robert W. Haile, and Duncan C. Thomas, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA; Charles F. Lynch, University of Iowa, General Hospital, Iowa City, IA; Kathleen E. Malone, Fred Hutchinson Cancer Research Center, Seattle, WA; Sharon N. Teraoka, Patrick Concannon, University of Virginia, Charlottesville, VA; Susan A. Smith, Marilyn Stovall, The University of Texas MD Anderson Cancer Center, Houston, TX; Lene Mellemkjær, Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; and Julia A. Knight, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

Abstract

PURPOSETo fully characterize the risk of contralateral breast cancer (CBC) in patients with breast cancer with a family history who test negative for BRCA1 and BRCA2 mutations. PATIENTS AND METHODSFrom our population-based case-control study comparing women with CBC to women with unilateral breast cancer (UBC), we selected women who tested negative for BRCA1 and BRCA2 mutations (594 patients with CBC/1,119 control patients with UBC). Rate ratios (RRs) and 95% CIs were estimated to examine the association between family history of breast cancer and risk of asynchronous CBC. Age- and family history-specific 10-year cumulative absolute risks of CBC were estimated.ResultsFamily history of breast cancer was associated with increased CBC risk; risk was highest among young women (< 45 years) with first-degree relatives affected at young ages (< 45 years; RR, 2.5; 95% CI, 1.1 to 5.3) or women with first-degree relatives with bilateral disease (RR, 3.6; 95% CI, 2.0 to 6.4). Women diagnosed with UBC before age 55 years with a first-degree family history of CBC had a 10-year risk of CBC of 15.6%. CONCLUSIONYoung women with breast cancer who have a family history of breast cancer and who test negative for deleterious mutations in BRCA1 and BRCA2 are at significantly greater risk of CBC than other breast cancer survivors. This risk varies with diagnosis age, family history of CBC, and degree of relationship to an affected relative. Women with a first-degree family history of bilateral disease have risks of CBC similar to mutation carriers. This has important implications for the clinical management of patients with breast cancer with family history of the disease.