Risk-reducing salpingo-oophorectomy and breast cancer incidence among Jewish BRCA1/BRCA2-mutation carriers-an Israeli matched-pair study

Objective To study the association of risk-reducing bilateral salpingo-oophorectomy (RRBSO) and breast cancer risk among BRCA pathogenic sequence variants (PSV). Methods Jewish Israeli BRCA carriers who underwent RRBSO were matched with those who did not-by the mutated gene and year of birth (+/- 1 year). Breast cancer rates were compared. Results Overall, 127 pairs met the inclusion criteria, 79 (60.6%) pairs harbored BRCA1 PSV and 50 (39.4%) pairs harbored BRCA2 PSV. Median follow up was 8.7 years (interquartile range 4.6-16.1 years). Breast cancer rate for all BRCA carriers combined was not affected by RRBSO (RRBSO 21 [16.5%] versus no RRBSO 31 [24.4%], hazard ratio [HR] for breast cancer 0.61, 95% confidence interval [CI] 0.33-1.14, P = 0.127). No association between RRBSO and breast cancer incidence was noted among BRCA1 PSV carriers. In BRCA2 PSV carriers, RRBSO was associated with a decreased overall breast cancer incidence (HR 0.20, 95% CI 0.44-0.91, P = 0.038), as well as after 5, 10, 15, and 20 years. Hormone replacement therapy was used by 62 PSV carriers, 52 in the RRBSO group and 10 in the no-RRBSO group and did not affect breast cancer risk (P = 0.463). Conclusion RRBSO is associated with breast cancer risk reduction in Jewish Israeli BRCA2 PSV carriers. Risk-reducing bilateral salpingo-oophorectomy was associated with breast cancer risk reduction in Jewish Israeli BRCA2 pathogenic sequence variant carriers.