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Clinical Management of BRCA Mutation Carriers


In a larger cohort of breast cancer patients (n = 336) from families with documented BRCA1/BRCA2 mutations and 9.2 years of follow-up, the rate of CBC was 28.9% at a mean interval of 5.5 years. Prior oophorectomy was associated with a 59% reduction in the risk of CBC.[263] Another case-control study of mutation carriers and noncarriers identified through ascertainment of women with bilateral breast cancer found that systemic adjuvant chemotherapy reduced CBC risk among mutation carriers (RR = 0.5, 95% CI, 0.2-1.0). Tamoxifen was associated with a nonsignificant risk reduction (RR = 0.7, 95% CI, 0.3-1.8). Similar risk reduction was seen in noncarriers; however, given the higher absolute CBC risk in carriers, there is potentially a greater impact of adjuvant treatment in risk reduction.[276] A high concordance in estrogen receptor status and tumor grade was reported among women from a registry of BRCA1/BRCA2 carriers who had bilateral breast cancer.[277] The German Consortium for Hereditary Breast and Ovarian Cancer estimated the risk for CBC in members of BRCA1 and BRCA2 mutation-positive families. At 25 years following the first breast cancer, the risk for CBC was close to 50% in both BRCA1 and BRCA2 families. The risk was also inversely correlated with age in this study, with the highest risks seen in women whose first breast cancer was before age 40 years. [230] A comparison of 655 women with BRCA1/BRCA2 mutations undergoing breast-conserving therapy versus those undergoing mastectomy noted that both treatment groups experienced high rates of CBC, exceeding 50% by 20 years of follow up. Rates were significantly higher among women with BRCA1 mutations compared with those with BRCA2 mutations, and among women whose first breast cancer occurred at or before age 35 years.[278] The WECARE study, a large population-based nested case-control study of CBC, reported a 10-year risk of CBC among BRCA1/BRCA2 mutation carriers of 15.9%, compared with a risk of 4.9% among noncarriers. Risks were also inversely related to age at first diagnosis in this study.[279]

Thus, despite differences in study design, study sites, and sample sizes, the data on CBC among women with BRCA1/BRCA2 mutations show several consistent findings:

  • The risk at all time points studied is significantly higher than that among sporadic controls.
  • The risk continues to rise with time since first breast cancer, and reaches 20% to 30% at 10 years of follow up, and 40% to 50% at 20 years in most studies.
  • Some, but not all, studies show an excess of CBC among BRCA1 carriers compared with BRCA2 carriers.
  • The risk for CBC is greatest among women whose first breast cancer occurs at a young age.



WebMD Public Information from the National Cancer Institute

Last Updated: May 16, 2012
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