The Effect of Risk-Reducing Salpingo-Oophorectomy on Breast Cancer Incidence and Histopathological Features in Women with a BRCA1 or BRCA2 Germline Pathogenic Variant

SIMPLE SUMMARY: Women with a BRCA1/2 germline pathogenic variant (GPV) are advised to undergo surgery to remove their ovaries and fallopian tubes at a young age to prevent tubal/ovarian cancer. This surgery is called a risk-reducing salpingo-oophorectomy (RRSO). Previous studies have suggested that RRSO may also decrease breast cancer (BC) risk by decreasing female hormone levels. The aim of this prospective study was to investigate the effect of RRSO on the risk and histopathological features of BCs in these women. We linked data from our hospital-based data/biobank to data from the Dutch Nationwide Pathology databank (PALGA). We included 1312 women in our study with 164 diagnosed BCs. RRSO did not influence BC incidence and there were no differences in histopathological features between BCs before and after RRSO. Therefore, the purpose of RRSO remains to decrease tubal/ovarian cancer risk only. ABSTRACT: Background: Risk-reducing salpingo-oophorectomy (RRSO) is advised for female BRCA1/2 germline pathogenic variant (GPV) carriers to reduce tubal/ovarian cancer risk. RRSO may also affect breast cancer (BC) incidence. The aim was to investigate the effect of RRSO on BC incidence and histopathological features in female BRCA1/2 GPV carriers. Methods: Prospectively collected clinical data from BRCA1/2 GPV carriers in our hospital-based data/biobank were linked to the Dutch Nationwide Pathology Databank (PALGA) in January 2022. Multivariable Cox-proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (95% CIs), where the pre-RRSO group was considered the reference group and the primary endpoint was the first primary BC. Histopathological features of BCs pre- and post-RRSO were compared using descriptive statistics. Results: In 1312 women, 164 incident primary BCs were observed. RRSO did not decrease BC risk for BRCA1 GPV (HR: 1.48, 95% CI: 0.91–2.39) or BRCA2 GPV (HR: 0.95, 95% CI: 0.43–2.07) carriers. BCs tended to be smaller post-RRSO (median: 12 mm) than pre-RRSO (15 mm, p: 0.08). There were no statistically significant differences in histopathological features. Conclusions: RRSO did not decrease BC risk or affect BC features in BRCA1/2 GPV in this study, although BCs diagnosed post-RRSO tended to be smaller.