Endocrine therapy and risk of cardiovascular disease and mortality in postmenopausal breast cancer survivors

Abstract

Background There are increasing concerns of cardiovascular safety related to endocrine therapy use in women with breast cancer (BC). We examined risk of cardiovascular disease (CVD) events and mortality associated with endocrine therapy use in postmenopausal women with early-stage BC. Methods Postmenopausal women diagnosed with stage I-III hormone receptor-positive BC from 2005 to 2013 were included (n = 8,495). Women were classified as aromatase inhibitor (AI) users, tamoxifen users, and non-users of endocrine therapy in the 12 months after BC diagnosis. Likelihood ratio tests examined whether the association of endocrine therapy use with CVD and mortality outcomes varied by body mass index (BMI) and history of CVD before BC diagnosis. Results Over a median follow-up of 7.5 years, women who used AIs were less likely to develop major adverse cardiovascular events (MACE) (HR = 0.84, 95% CI: 0.73-0.97) and heart failure (HR = 0.81, 95% CI: 0.66-0.99) compared with non-users of endocrine therapy. No associations between tamoxifen use and CVD outcomes were observed. AI use was associated with lower risk all-cause, CVD-related, and non-CVD-related mortality, compared with non-use of endocrine therapy. Tamoxifen use was associated with lower risk of all-cause mortality and non-CVD-related mortality, compared with non-use of endocrine therapy, and the association was modified by BMI (P for interaction <0.05). Conclusion Our findings suggest endocrine therapy use reduces all-cause mortality risk and may not increase CVD risk in postmenopausal women with early-stage hormone receptor-positive BC.