Time trends, uptake, and oncological effects of risk-reducing surgeries in 3067 Danish BRCA1/2 carriers: a population-based study with matched controls.

Knowledge of the uptake and breast and ovarian cancer-preventive and survival effects of bilateral risk-reducing mastectomy (BRRM) and salpingo-oophorectomy (RR-BSO) in female BRCA1/2 carriers is essential for optimized decision-making. This study aimed to examine time trends in the number of registered unaffected BRCA1/2 carriers, BRRM and RR-BSO uptake, and oncological effects of risk-reducing surgeries in a nationwide Danish cohort with matched controls. We included 3067 female BRCA1/2 carriers registered in the Hereditary Breast and Ovarian Cancer Registry and 30,652 age-matched controls between 2000 and 2022. Data were retrieved from national health registries. Uptake and oncological effects of risk-reducing surgeries were assessed using cumulative incidences and Cox proportional hazards models with 95% confidence intervals (CI). Annual numbers of registered unaffected BRCA1/2 carriers, BRRM, and RR-BSO increased over time. BRRM and RR-BSO uptake 10 years after genetic test varied with the age at genetic test and parity. BRRM reduced the hazard rate of breast cancer by 94% [hazard ratio (HR) 0.06, CI 0.01-0.25]. The same pattern was not found for RR-BSO (HR = 1.31, CI 0.90-1.91). Compared to controls, BRCA1/2 carriers had an increased hazard rate for breast cancer before BRRM (HR 7.49, CI 5.81-9.42). BRRM's large protective effect against breast cancer in BRCA1/2 carriers was confirmed, in contrast to that of RR-BSO. There were tendencies toward a reduction in overall mortality rates after BRRM, and compared with controls, we saw tendencies toward higher mortality rates before BRRM.