A new study that used prospective data provides estimates of cancer risk based on BRCA1/2 mutation status and shows the potential role of family history and the location of the mutation in assessing risk.
The study, published in JAMA, estimated that the cumulative breast cancer risk to age 80 is 72% for BRCA1 mutation carriers, and 69% for BRCA2 carriers. For ovarian cancer, the cumulative risk to age 80 is 44% for BRCA1 mutation carriers, and 17% for BRCA2 carriers.
“Because the study mainly included unaffected women identified by mutation screening based on cancer family history, early age at onset of a family member, or both, the overall estimates are relevant to mutation carriers identified through clinical testing,” wrote Karoline B. Kuchenbaecker, PhD, of the Centre for Cancer Genetic Epidemiology at the University of Cambridge, England, and colleagues.
According to the study, age-specific cancer risk estimates can be used to help women with BRCA1 and BRCA2 mutations make informed decisions about cancer screening. With this study, the researchers sought to estimate age-specific risks for breast, ovarian, and contralateral breast cancer using data from a large prospective cohort.
From 1997 to 2011 the prospective study recruited 6,036 BRCA1 and 3,820 BRCA2 female mutations carriers. The cohort included 5,046 unaffected carriers and 4,810 with breast, ovarian, or both cancers. The majority of patients were from large national studies in the United Kingdom, the Netherlands, and France. The median follow-up was 5 years.
Of the 3,886 women eligible for breast cancer analysis, 426 were diagnosed with breast cancer; for the 5,066 women eligible for ovarian cancer analysis, 109 were diagnosed with ovarian cancer; and for the 2,213 eligible for contralateral breast cancer analysis, 245 were diagnosed during follow-up.
Data indicated that the incidence of breast cancer increased rapidly until ages 30 to 40 for BRCA1 carriers and until ages 40 to 50 for BRCA2 carriers. After those ages, the incidence remained constant until age 80.
“The estimated breast and ovarian cancer risks were consistent with findings from retrospective family-based studies,” the researchers wrote. “The breast cancer standardized incidence ratios decreased with increasing age for both BRCA1 and BRCA2 carriers, but the estimates were higher than those previously reported for younger age groups.”
For contralateral breast cancer, the cumulative risk 20 years after the breast cancer diagnosis was 40% for BRCA1 carriers and 26% for BRCA2 carriers.
“The contralateral breast cancer analysis also included women diagnosed as having breast cancer prior to study recruitment,” the researchers noted. “The inclusion of survivors could potentially bias the estimation of contralateral breast cancer risks if such risks were related to the outcome of the first cancer; however, there is no strong evidence of such a relationship in the general population. Furthermore, the results were similar after excluding women whose first breast cancer diagnosis occurred more than 5 years prior to study recruitment, suggesting that any bias is likely to be small.”
Looking at women with a family history, the researchers found that breast cancer risk increased with the increasing number of first- and second-degree relatives diagnosed with breast cancer for BRCA1 (hazard ratio [HR] for 2 or more relatives vs 0, 1.99; P < .001 for trend) and BRCA2 carriers (HR, 1.91; P = .02 for trend).
Finally, risk for breast cancer was higher if mutations were located outside compared with within the regions bounded by positions c.2282–c.4071 in BRCA1 (HR, 1.46; 95% CI, 1.11–1.93; P = .007) and c.2831–c.6401 in BRCA2 (HR, 1.93; 95% CI, 1.36–2.74; P < .001).