Breast Cancer Risk for Noncarriers of Family-Specific BRCA1 and BRCA2 Mutations: Findings From the Breast Cancer Family Registry.

Kurian AW, Gong GD, John EM, Johnston DA, Felberg A, West DW, Miron A, Andrulis IL, Hopper JL, Knight JA, Ozcelik H, Dite GS, Apicella C, Southey MC, Whittemore AS.

Source

Allison W. Kurian, Gail D. Gong, Esther M. John, David A. Johnston, Anna Felberg, Dee W. West, and Alice S. Whittemore, Stanford University School of Medicine, Stanford; Esther M. John and Dee W. West, Cancer Prevention Institute of California, Fremont, CA; Alexander Miron, Dana-Farber Cancer Institute, Boston, MA; Irene L. Andrulis, Julia A. Knight, and Hilmi Ozcelik, Samuel Lunenfeld Research Institute, Mount Sinai Hospital; Irene L. Andrulis and Hilmi Ozcelik, University of Toronto; Irene L. Andrulis, Cancer Care Ontario, Toronto, Ontario, Canada; and John L. Hopper, Gillian S. Dite, Carmel Apicella, and Melissa C. Southey, University of Melbourne, Melbourne, Victoria, Australia.

Abstract

PURPOSEWomen with germline BRCA1 and BRCA2 mutations have five- to 20-fold increased risks of developing breast and ovarian cancer. A recent study claimed that women testing negative for their family-specific BRCA1 or BRCA2 mutation (noncarriers) have a five-fold increased risk of breast cancer. We estimated breast cancer risks for noncarriers by using a population-based sample of patients with breast cancer and their female first-degree relatives (FDRs). PATIENTS AND METHODSPatients were women with breast cancer and their FDRs enrolled in the population-based component of the Breast Cancer Family Registry; patients with breast cancer were tested for BRCA1 and BRCA2 mutations, as were FDRs of identified mutation carriers. We used segregation analysis to fit a model that accommodates familial correlation in breast cancer risk due to unobserved shared risk factors. RESULTS: relative risk was 0.39 (95% CI, 0.04 to 3.81). Residual breast cancer correlation within families was strong, suggesting substantial risk heterogeneity in women without BRCA1 or BRCA2 mutations, with some 3.4% of them accounting for roughly one third of breast cancer cases. CONCLUSIONThese results support the practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA1 or BRCA2 mutation.