Endocrine therapy adherence and 10-year cardiometabolic risk in hormone receptor-positive breast cancer

Adjuvant endocrine therapy (AET) reduces breast cancer (BC) recurrence but may adversely affect cardiometabolic health. We evaluated the association between AET adherence duration and 10-year risk of hypertension, dyslipidemia, diabetes, and mortality among postmenopausal women with early-stage hormone receptor-positive BC.

We conducted a prospective cohort study of 8,365 postmenopausal women with stage I-III hormone receptor-positive BC within Kaiser Permanente Northern California who initiated AET between 2005 and 2013. Adherence (proportion of days covered >80%) was assessed annually using prescription dispensing data. We estimated 10-year cumulative incidence (CI) under six adherence duration strategies (0-5 years) using sequentially doubly robust estimation, adjusting for demographic, clinical, lifestyle, and tumor characteristics. Analyses were stratified by AET type (aromatase inhibitor [AI]; tamoxifen [TAM]).

Overall, 42.7% were adherent for ≥5 years. Compared with nonadherence, 5-year adherence was associated with higher 10-year CI of hypertension (absolute CI difference = 8.81% [95% confidence interval (CI): 4.25-13.4]), dyslipidemia (5.16% [0.31-10.0]), and diabetes (2.58% [0.02-5.14]), but lower all-cause death (10.7% [7.74-13.7]) and BC-specific death (5.37% [3.36-7.38]). Five-year AI adherence was associated with increased hypertension (9.37% [4.54-14.2]), dyslipidemia (6.84% [1.76-11.9]), and diabetes (3.29% [0.58-6.00]), whereas TAM adherence was associated only with hypertension (9.37% [4.54-14.2]). AI adherence was associated with higher dyslipidemia risk than TAM (9.86% [5.09-14.6]).

AI adherence was associated with increased cardiometabolic risk, whereas TAM was associated only with hypertension risk. Despite these risks, AET was associated with improved survival. Further research should evaluate whether cardiometabolic risk factors influence cardiovascular events among BC survivors.