Risk assessment for developing cancer based on BRCA1 and BRCA2 mutation carrier status could be affected by family history and location of the mutation, a study published in JAMA has found.

The researchers prospectively estimated age-specific risks of developing breast, ovarian, and contralateral breast cancer in BRCA1 and BRCA2 mutation carriers to improve understanding of best clinical management of mutation carriers.

From 1997 to 2011, researchers recruited 6036 BRCA1 and 3820 BRCA2 female carriers. Of these carriers, 5046 were unaffected and 4810 had breast or ovarian cancer or both at baseline. Most participants were from large national studies in the United Kingdom, the Netherlands, and France. Median follow-up was 5 years, and follow-up ended December 2013.

Among 3886 women eligible for breast cancer analysis, 5066 women eligible for ovarian cancer analysis, and 2213 women eligible for contralateral breast cancer analysis, breast cancer was diagnosed in 426 women, ovarian cancer in 109 women, and contralateral breast cancer in 245 women during follow-up.

The cumulative risk of breast cancer to age 80 years was 72% for carriers of BRCA1 and 69% for carriers of BRCA2. Incidence of breast cancer increased quickly from early adulthood to 30 to 40 years for BRCA1 carriers and from early adulthood to 40 to 50 years for BRCA2 carriers, at which point incidence remained constant until age 80 years (20 to 30 per 1,000 person-years).

The cumulative risk of ovarian cancer to age 80 years was 44% for carriers of BRCA1 and 17% for carriers of BRCA2. The cumulative risk of contralateral breast cancer 20 years after a breast cancer diagnosis was 40% for carriers of BRCA1 and 26% for carriers of BRCA2.

The risk of developing breast cancer increased with more first-degree and second-degree relatives with breast cancer for both BRCA1 (P <.001 for trend) and BRCA2 (P =.02 for trend).

Additionally, the risk of developing breast cancer was greater if mutations were located outside the regions bounded by positions c.2282-c.4071 in BRCA1 (P =.007) and c.2831-c.6401 in BRCA2 (P <.001).

Reference

1. Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers [published online June 20, 2017]. JAMA. doi: 10.1001/jama.2017.7112