Refining Estimates of Risk for Breast and Ovarian Cancer in BRCA1 and BRCA2 Carriers

Virginia Kaklamani, MD

The largest-ever prospective study sheds light on the magnitude of risk and predictive influence of breast cancer susceptibility alleles.

Several studies have addressed risk for breast cancer (BC) and ovarian cancer (OC) in BRCA1 and BRCA2 carriers, but most have been retrospective, yielding large variations in estimated risks. Now, U.K. investigators have conducted a large, prospective study of risk for BC and OC in a cohort of 978 BRCA1 carriers and 909 BRCA2 carriers. Several single nucleotide polymorphisms (SNPs) affect breast cancer risk. Eleven of these were selected and risk scores were calculated for BRCA1 and BRCA2 carriers.

Among BRCA1 carriers, average cumulative risk by age 70 was 60% for BC, 83% for contralateral BC, and 59% for OC. In BRCA2 carriers, cumulative risks were 55% for BC, 62% for contralateral BC, and 16% for OC. BC incidence peaked at age 50 to 59 in BRCA1 carriers and at age 40 to 49 in BRCA2 carriers. BC risk estimates were higher when follow-up stopped at oophorectomy. OC incidence peaked at age 60 to 69 in both BRCA1 and BRCA2 carriers. Among BRCA2 carriers, cumulative risk for BC by age 70 was 72% for those in the highest SNP-based risk tertile versus 20% for those in the lowest tertile.

Citation(s):

Mavaddat N et al. Cancer risks for BRCA1 and BRCA2 mutation carriers: Results from prospective analysis of EMBRACE. J Natl Cancer Inst 2013 Jun 5; 105:812.