Long-term health outcomes of bilateral salpingo-oophorectomy in BRCA1 and BRCA2 pathogenic variant carriers with personal history of breast cancer: a retrospective cohort study using linked electronic health records

BACKGROUND: Carriers of BRCA1 and BRCA2 pathogenic variants are at elevated risk of developing breast and ovarian cancers. To mitigate ovarian cancer risk, bilateral salpingo-oophorectomy (BSO) is commonly recommended for unaffected carriers and those with personal breast cancer history. Assessing BSO's long-term health outcomes in carriers with previous breast cancer history is essential. This study aims to examine the association between BSO and long-term health outcomes in individuals carrying pathogenic variants in BRCA1 and BRCA2 and with personal history of breast cancer. METHODS: Data from the National Cancer Registration Dataset (NCRD) were linked with data from genetic testing laboratories to identify carriers of BRCA1 and BRCA2 pathogenic variants affected by breast cancer using pseudonymised patient identifiers. Further linkage to the Hospital Episode Statistics-Admitted Patient Care (HES-APC) dataset identified patients who had undergone BSO. Women aged 20-75 years, with a diagnosis of breast cancer as their first primary malignancy in 1995-2019 were eligible. Long-term health outcomes were identified from HES-APC and NCRD. Missing data were imputed using multivariate imputations by chained equations. Multivariable Cox regression was used to examine the associations with mortality (all-cause mortality, breast cancer-specific mortality, and non-breast cancer-specific mortality), second non-breast cancer, cardiovascular diseases, ischaemic heart disease, cerebrovascular diseases, contralateral breast cancer, and depression. Analyses were adjusted for age at diagnosis, diagnosis year, ethnicity, deprivation index, tumour characteristics, Charlson comorbidity index, cancer treatment, and second cancer diagnosis before the start of follow-up. FINDINGS: We included 1674 BRCA1, 1740 BRCA2, and nine BRCA1 and BRCA2 carriers who were diagnosed with breast cancer between 1995 and 2019, with median follow-up time of 5·5 years (IQR 3·4-8·2). The study population (n=3423) consisted of 3002 (88·7%) White, 170 (5·0%) Asian, 59 (1·7%) Black, 26 (0·8%) mixed, and 74 (2·2%) other ethnic groups, and 92 (2·7%) had missing ethnicity. The uptake of BSO was significantly lower among Black women (odds ratio [OR] vs White women 0·48, 95% CI 0·34-0·67), and Asian women (0·47, 0·27-0·82). BSO uptake was higher in women living in the least socioeconomically deprived areas (OR vs most deprived 1·38, 95% CI [1·10-1·72]). BSO was associated with a reduced risk of all-cause mortality for both BRCA1 and BRCA2 pathogenic variant carriers (HR 0·52, 95% CI 0·41-0·64) and reduced breast cancer-specific mortality (BRCA1: HR 0·62, 95% CI 0·42-0·92 and BRCA2: 0·48, 0·34-0·68). It was also associated with a reduced risk of second non-breast cancer in the combined BRCA1 and BRCA2 sample (HR 0·59, 95% CI 0·37-0·94). There BSO was not associated with increased risk of cardiovascular diseases (HR 0·73, 95% CI 0·53-1·01), ischaemic heart disease (1·04, 0·48-2·26), cerebrovascular disease (0·32, 0·11-0·90), non-breast cancer specific mortality (0·72, 0·45-1·16), contralateral breast cancer (1·18, 0·64-2·16), or depression (0·94, 0·62-1·42). INTERPRETATION: The evidence supports offering BSO to BRCA1 and BRCA2 pathogenic variant carrriers with a personal history of breast cancer, as they appear to benefit from having the procedure, without evidence of an increased risk of adverse long-term health outcomes. FUNDING: Cancer Research UK.