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

Publication Number: 320

Background: Although endocrine therapy is an effective treatment for breast cancer, its antiestrogen effects are associated with increased risks of cardiovascular diseases (CVDs) and type 2 diabetes (T2DM). Previous studies have investigated their antiestrogen roles on CVDs and T2DM in only for elderly breast cancer patients, and studies that reflect the characteristics of breast cancer patients in Korea are necessary. Thus, further studies considering various age groups and ethnic differences are required.

Objectives: This study aimed to investigate the associations between endocrine therapy and the risks of CVDs and T2DM among breast cancer patients in Korea.

Methods: Using a retrospective cohort design, we included breast cancer patients aged over 20 years old from the National Health Insurance Service database of Korea. Total 144,866 and 138,311 patients were included for the composite of CVDs and T2DM outcomes, respectively. The mean follow-up duration of the study population was 5.3 (SD: 3.1) years. Endocrine therapy was treated as time-varying exposure and categorized by nonusers, selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), and both users. Composite of CVDs included stroke, coronary heart diseases (CHD), venous thromboembolism (VTE), heart failure, and arrhythmia. Time-dependent Cox regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). Age at diagnosis, socioeconomic status, histological type, other treatments, and comorbidities were adjusted in the model.

Results: Compared to nonusers, SERMs were associated with increased risks of stroke [HR (95% CI): 1.23 (1.07-1.41)] and VTE [1.72 (1.33-2.23)], while AIs were associated with increased risks of stroke [1.16 (1.01-1.33)] and CHD [1.24 (1.10-1.39)]. The risk of T2DM was associated with SERMs [1.23 (1.15-1.32)], AIs [1.21 (1.12-1.30)], and dual exposures [1.27 (1.14-1.41)]. These associations particularly remained in breast cancer patients younger than age 55 or premenopausal patients. As with the results that compared to nonusers, AI users had a higher risk of CHD [1.18 (1.04-1.33)] and a lower risk of VTE [0.73 (0.56-0.96)] than SERM users.

Conclusions: In breast cancer patients of Korea, endocrine therapy was associated with increased risks of CVDs and T2DM. The monitoring of cancer comorbidities after endocrine therapy is needed for younger patients as well as older patients.