Effects of Endocrine Therapy on Cardiovascular Diseases and Type 2 Diabetes Among Breast Cancer Survivors: The National Health Insurance Service Database of Korea

BACKGROUND: Although endocrine therapy is an effective treatment for breast cancer, its antiestrogen effects are associated with increased risks of cardiovascular diseases and type 2 diabetes. This study aimed to investigate the association between endocrine therapy and the risk of cardiovascular diseases and type 2 diabetes among breast cancer survivors in Korea, in consideration of various age groups. METHODS AND RESULTS: In the National Health Insurance Service database of Korea, a total of 133 171 patients with breast cancer aged ≥20 years were included in the current study. Endocrine therapy was treated as time‐varying exposure, and patients were categorized as nonusers, selective estrogen receptor modulator users, aromatase inhibitor users, and both users. Time‐dependent Cox regression models were used to estimate hazard ratios (HRs) and 95% CIs. Age at diagnosis, socioeconomic status, histological type, other treatments, and comorbidities were adjusted in the model. Compared with nonusers, selective estrogen receptor modulator users were associated with higher risks of stroke (HR, 1.20 [95% CI, 1.04–1.40]) and venous thromboembolism (HR, 1.47 [95% CI, 1.13–1.90]), whereas aromatase inhibitor users were associated with a higher risk of coronary heart disease (HR, 1.22 [95% CI, 1.06–1.41]). The risk of type 2 diabetes was associated with selective estrogen receptor modulator users (HR, 1.13 [95% CI, 1.05–1.21]), aromatase inhibitor users (HR, 1.14 [95% CI, 1.05–1.23]), and both users (HR, 1.24 [95% CI, 1.10–1.39]). In particular, the risk of a composite of cardiovascular diseases was higher in younger or premenopausal patients. CONCLUSIONS: In breast cancer survivors in Korea, endocrine therapy is associated with a higher risk of cardiovascular diseases and type 2 diabetes. Monitoring of cancer comorbidities after endocrine therapy is needed in younger and older patients.