Menopausal hormone therapy after a diagnosis of breast cancer in women with a <i>BRCA</i> pathogenic variant and risk of death.

10506 Background: Use of menopausal hormone therapy (MHT) is contraindicated for women with a personal history of breast cancer. This topic is of importance among women with a pathogenic or likely pathogenic variant (mutation) in BRCA1 or BRCA2 given their tendency to develop early onset disease as well as the recommendation to undergo oophorectomy prior to natural menopause. Methods: We conducted a prospective analysis of MHT use following breast cancer in BRCA carriers and the risk of death. The study included BRCA carriers with a diagnosis of breast cancer, no history of another cancer, no prior MHT use, and who were enrolled in a longitudinal study. Women who initiated MHT after their diagnosis were matched to women who did not use MHT on year of birth, age of diagnosis, and treatments received – resulting in 183 matched pairs. We followed women from the date of first MHT use in the exposed and the matched date in the unexposed. Cox proportional hazards was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for the risk of death associated with MHT use. Results: Among the 183 MHT users, 53 (29%) used a local MHT and 130 (71%) used a systemic MHT. After 6.0 years of follow-up (range 0.01-22.7); there were 9 (4.9%) deaths in the MHT group vs. 22 deaths (12%) in the no MHT group ( P = 0.01). The corresponding number of breast cancer deaths were 6 (3.3%) vs. 16 (8.7%) ( P = 0.03). The HR for all-cause mortality was 0.31 (95%CI 0.14-0.69; P = 0.004) and for breast cancer-specific mortality was 0.27 (95%CI 0.10-0.70; P = 0.007). The corresponding risk estimates for all-cause death by invasiveness were 0.25 (95%CI 0.11-0.61; P = 0.002) and 0.54 (95%CI 0.07-4.02; P = 0.54) for invasive disease and DCIS, respectively. All-cause mortality with use of systemic MHT was 0.27 (95%CI 0.11-0.67; P = 0.005) and was 0.19 (95%CI 0.03-1.45; P = 0.11) for local MHT. Compared to never HRT use, the HR for E-alone was 0.35 (0.12-1.02; P = 0.05) and was 0.58 (95%CI 0.08-4.29; P = 0.59) for E+P. Subgroup analyses by formulation, gene mutation and tumour pathology are on-going. Conclusions: Although based on small strata, the preliminary findings are suggestive of no increased risk of death with MHT use after BRCA -breast cancer and may offer an opportunity to improve quality of life in this unique population. Replication in larger datasets are needed.