Abstract 1285: Endocrine therapy adherence and 10-year risk of cardiometabolic outcomes among women with hormone receptor-positive breast cancer

Abstract Background: Adjuvant endocrine therapy (ET) reduces breast cancer (BC) recurrence and mortality but may adversely affect cardiometabolic health. We evaluated, for the first time, the association between ET adherence duration and 10-year cumulative incidence (CI) of hypertension, dyslipidemia, and diabetes among women with hormone receptor-positive BC. Methods: 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 ET between 2005 and 2013. Adherence was categorized annually over five years and summarized into adherence durations from 0 to 5 years. Cardiometabolic outcomes were identified from diagnoses, labs, and medication dispensings. We estimated 10-year CI under varying adherence durations using sequentially doubly robust (SDR) estimation with Super Learner to flexibly model treatment and outcome mechanisms. Analyses accounted for all-cause death as a competing risk and stratified by ET type (aromatase inhibitor [AI] vs tamoxifen [TAM]). Results: Overall, 40.8% were adherent for ≥5 years. Compared with never-adherent women, those adherent for ≥5 years were younger (aged 50-70: 73.7% vs 64.0%), lived in higher-income neighborhoods ($80,395 vs $70,417), more often received chemotherapy (34.1% vs 20.9%), and less likely to smoke (5.92% vs 10.5%). Among women never adherent, adjusted 10-year CI of hypertension, dyslipidemia, and diabetes were 22.7% (20.6-24.9), 25.6% (23.3-27.8), and 8.91% (7.65-10.2). Among those adherent for 5 years, CI were 29.1% (27.0-31.2), 32.4% (30.3-34.6), and 12.6% (11.5-13.8), corresponding to CI differences of 6.37% (3.36-9.37), 6.83% (3.79-9.94), and 3.73% (2.06-5.40). CI generally increased with each additional year of adherence. In ET-stratified analyses, 5-year AI adherence was associated with hypertension (CI difference=6.85% [3.74-10.0]), dyslipidemia (8.32% [4.94-11.7]), and diabetes (4.21% [2.28-6.13]) compared with those never adherent. TAM adherence was associated only with hypertension (5.83% [0.53-11.1]). Compared directly with TAM, AI adherence resulted in higher CI of dyslipidemia (difference=10.2% [4.33-16.1]) and diabetes (2.96% [0.07-5.85]). Conclusion: Longer adherence to AIs was associated with increased 10-year risk of hypertension, dyslipidemia, and diabetes, while TAM use was associated only with elevated hypertension risk. With over 4.3 million breast cancer survivors in the US, findings highlight the need for further research to optimize patient selection for ET, balancing BC benefits with potentially higher cardiovascular disease risk, and strategies for early cardiometabolic management during ET. Citation Format: Jorge R. Ledesma, Joshua Nugent, Cecile A. Laurent, Samir R. Thadani, Richard K. Cheng, Jennifer M. Specht, Janise M. Roh, Raymond Liu, Heather Greenlee, Marilyn L. Kwan. Endocrine therapy adherence and 10-year risk of cardiometabolic outcomes among women with hormone receptor-positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1285.