Study Estimates Risks of Breast and Ovarian Cancers in BRCA1/2-Mutation Carriers

In a prospective cohort study reported in JAMA, Kuchenbaecker et al derived estimates of cumulative risks for breast, ovarian, and contralateral breast cancers among women carrying BRCA1 or BRCA2 mutations.

Study Details

The study involved data from 6,036 BRCA1 and 3,820 BRCA2 carriers recruited between 1997 and 2011 through the International BRCA1/2 Carrier Cohort Study, Breast Cancer Family Registry, and Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer. Of them, 5,046 women were unaffected, and 4,810 had breast or ovarian cancer or both at baseline. The majority of women were from large national studies in the UK, Netherlands, and France. Follow-up ended in December 2013.

Cancer Risks

A total of 3,886 women (median age = 38 years), 5,066 women (median age = 38 years), and 2,213 women (median age = 47 years) were eligible for the breast cancer, ovarian cancer, and contralateral breast cancer analyses, respectively. Median follow-up was 5 years. During follow-up, 426 patients were diagnosed with breast cancer, 109 were diagnosed with ovarian cancer, and 245 were diagnosed with contralateral breast cancer.

  • The cumulative risk of breast cancer to age 80 years was 72% for BRCA1 and 69% for BRCA2 carriers. The incidence rose rapidly in early adulthood until ages 30 to 40 years for BRCA1 and 40 to 50 years for BRCA2 carriers and then remained at a constant rate of 20 to 30 cases per 1,000 person-years until age 80 years.
  • The cumulative risk of ovarian cancer to age 80 years was 44% for BRCA1 and 17% for BRCA2 carriers.
  • The cumulative risk for contralateral breast cancer at 20 years after breast cancer diagnosis was 40% for BRCA1 and 26% for BRCA2 carriers.
  • The breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed with breast cancer for both BRCA1 (hazard ratio [HR] for ≥ 2 vs 0 affected relatives = 1.99, P < .001 for trend) and BRCA2 carriers (HR for ≥ 2 vs 0 affected = 1.91, P = .02 for trend).
  • The breast cancer risk was increased with mutations located outside vs within regions bounded by positions c.2282-c.4071 in BRCA1 (HR = 1.46, P = .007) and c.2831-c.6401 in BRCA2 (HR = 1.93, P < .001).

The investigators concluded: “These findings provide estimates of cancer risk based on BRCA1 and BRCA2 mutation carrier status using prospective data collection and demonstrate the potential importance of family history and mutation location in risk assessment.”

The study was supported by Cancer Research UK grants.

Antonis C. Antoniou, PhD, of the University of Cambridge, is the corresponding author of the JAMA article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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