Cardiovascular Disease With Hormone Therapy and Ovarian Suppression in Premenopausal Breast Cancer Survivors.

Background: Hormone therapies, including aromatase inhibitors and tamoxifen, are used with ovarian suppression to improve outcomes in premenopausal patients with breast cancer. Cardiovascular impacts of these treatments among premenopausal women are unknown. Objectives: The aim of this study was to test the hypothesis that the use of aromatase inhibitors in combination with ovarian suppression, relative to tamoxifen, is associated with greater incident cardiovascular disease (CVD) risk in premenopausal breast cancer survivors. Methods: The MarketScan administrative claims databases (2013-2020) were used to identify enrollees younger than 55 years who had incident breast cancer and were treated with either an aromatase inhibitor and ovarian suppression or tamoxifen. Propensity score matching was used to balance treatment groups across confounding variables including age, breast cancer treatments, and comorbidities. The HR for CVD (including atrial fibrillation, myocardial infarction, stroke, heart failure hospitalization, angina, or coronary revascularization) was calculated by treatment group. Results: In the matched cohort, over a median follow-up time of 1.55 years, the incidence rate was 2.3 per 100 person-years among users of aromatase inhibitors plus ovarian suppression (51 CVD events in 2,205 person-years) and 1.0 per 100 person-years for tamoxifen users (102 CVD events in 9,913 person-years). Users of aromatase inhibitors plus ovarian suppression had a 2.20-fold higher hazard of CVD than tamoxifen users (HR: 2.20; 95% CI: 1.57-3.09). In absolute terms, the incidence rate difference was 0.012 (95% CI: 0.006-0.019). Findings were robust to several sensitivity analyses. Conclusions: Premenopausal patients with breast cancer treated with aromatase inhibitors and ovarian suppression may be at elevated risk for CVD and should be monitored for cardiovascular risk.