Researchers have estimated the age-specific risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers, according to a study published in JAMA.

Karoline B. Kuchenbaecker, PhD, from the Department of Public Health and Primary Care at the University of Cambridge in England, and colleagues, conducted a prospective cohort study of 6036 BRCA1 and 3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian cancer or both at baseline). The women were recruited in 1997-2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry, and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, with ascertainment through family clinics (94%) and population-based studies (6%). Follow-up ended in December 2013.

The authors identified BRCA1/2 mutations, family cancer history, and mutation location throughout the study. The primary outcome was annual incidences, standardized incidence ratios, and cumulative risks of breast, ovarian, and contralateral breast cancer.

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A total of 3886 women (median age, 38 years) were eligible for the breast cancer analysis, 5066 women (median age, 38 years) were eligible for the ovarian cancer analysis, and 2213 women (median age, 47 years) were eligible for the contralateral breast cancer analysis. Of these women, 426 were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer during follow-up.

The cumulative breast cancer risk to age 80 was 72% for BRCA1 and 69% for BRCA2 carriers. Breast cancer incidences increased rapidly in early adulthood until ages 30 to 40 years for BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a similar, constant incidence (20-30 per 1000 person-years) until age 80 years.

The cumulative ovarian cancer risk to age 80 years was 44% for BRCA1 and 17% for BRCA2 carriers. For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% for BRCA1 and 26% for BRCA2 carriers (hazard ratio [HR] for comparing BRCA2 vs BRCA1, 0.62).

Breast cancer risk increased with a larger number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for >2 vs 0 affected relatives, 1.99) and BRCA2 carriers (HR, 1.91). Breast cancer risk was higher if mutations were located outside vs within the regions bounded by positions c.2282-c.4071 in BRCA1 (HR, 1.46) and c.2831-c.6401 in BRCA2 (HR, 1.93).

“These findings provide information on cancer risk for BRCA1 and BRCA2 mutation carriers using prospective data and demonstrate the potential importance of family history and mutation location in risk assessment,” stated the authors.


  1. Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA. 20 June 2017. doi: 10.1001/jama.2017.7112