Uptake and Effectiveness of Risk-Reducing Surgeries in Unaffected Female BRCA1 and BRCA2 Carriers: A Single Institution Experience in the Czech Republic

SIMPLE SUMMARY: Women with BRCA 1/2 pathogenic/likely pathogenic variants (P/LPVs) have a high lifetime risk of developing breast and ovarian cancer. The aim of the retrospective study is to analyze the rate, longitudinal trends, and effectiveness of prophylactic risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO) on the incidence of breast and ovarian cancer. We analyzed data from 496 unaffected BRCA1/2 carriers with a median follow-up of 6.0 years. A statistically significant increase of RRM (12% vs. 29%) and RRSO (31% vs. 42%) was observed when comparing periods 2005–2012 and 2013–2020 (p < 0.001). BC developed in 15.9% of BRCA1/2 carriers without RRM vs. 0.6% of BRCA1/2 carriers after RRM (HR 20.18, p < 0.001). OC was diagnosed in 4.3% vs. 0% of BRCA1/2 carriers without vs. after RRSO (p < 0.001). Data shows a high effectiveness and significant increase of prophylactic surgeries over 20 years period in a central European population of BRCA1/2 carriers. ABSTRACT: Unnafected female carriers of BRCA1 and BRCA2 pathogenic/likely pathogenic variants (P/LPVs) are at higher risk of breast cancer (BC) and ovarian cancer (OC). In the retrospective single-institution study in the Czech Republic, we analyzed the rate, longitudinal trends, and effectiveness of prophylactic risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) on the incidence of BC and OC in BRCA1/2 carriers diagnosed between years (y) 2000 to 2020. The study included 496 healthy female BRCA1/2 carriers. The median follow-up was 6.0 years. RRM was performed in 156 (31.5%, mean age 39.3 y, range 22–61 y) and RRSO in 234 (47.2%, mean age 43.2 y, range 28–64 y) BRCA1/2 carriers. A statistically significant increase of RRM (from 12% to 29%) and RRSO (from 31% to 42%) was observed when comparing periods 2005–2012 and 2013–2020 (p < 0.001). BC developed in 15.9% of BRCA1/2 carriers without RRM vs. 0.6% of BRCA1/2 carriers after RRM (HR 20.18, 95% CI 2.78- 146.02; p < 0.001). OC was diagnosed in 4.3% vs. 0% of BRCA1/2 carriers without vs. after RRSO (HR not defined due to 0% occurrence in the RRSO group, p < 0.001). Study results demonstrate a significant increase in the rate of prophylactic surgeries in BRCA1/2 healthy carriers after 2013 and the effectiveness of RRM and RRSO on the incidence of BC and OC in these populations.