A multi-center study to evaluate the impact of germline BRCA1 and BRCA2 mutations on ovarian cancer survival

Background

Approximately 10 percent of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. However, the impact of these mutations on ovarian cancer prognosis remains unclear.

Methods

We performed an international multi-center study of 1,470 EOC cases with pathogenic germline mutations in BRCA1 (1,134) or BRCA2 (336) and 2,814 non-carriers. Our goal was to further characterize the survival of BRCA carriers with EOC compared to non-carriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. Cox proportional hazards regression, both unadjusted and adjusted for other prognostic variables, was used to measure differences in overall survival during the five years following diagnosis.

Results

The five-year overall survival was 36 percent for non-carriers, 44 percent for BRCA1 carriers and 52 percent for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 carriers showed a more favorable survival than non-carriers (BRCA1, HR=0.78; 95% CI=0.68-0.89, P=2x10^-4; BRCA2, HR = 0.61; 95% CI=0.50-0.76, P=6x10^-6;). These survival differences remained after adjustment for stage, grade, histology and age at diagnosis (BRCA1, HR=0.73, 95% CI=0.64-0.84, P=2x10^-5; BRCA2, HR = 0.49, 95% CI=0.39-0.61, P=3x10^-10).

Conclusions

We observed a significantly improved survival in germline BRCA1 and BRCA2 mutation carriers with EOC compared to non-carriers. BRCA2 carriers had the most favorable outcome with a distinct clinical course from BRCA1 carriers. The magnitude of the differences we observed highlight the need for clinical trials in EOC to be stratified by BRCA1/2 status and suggest that the routine testing of women presenting with high-grade serous EOC may be warranted.