0077Aromatase Inhibitors Versus Tamoxifen and Cardiovascular-Kidney-Metabolic Stage Progression in Women with Breast Cancer: A Real-World Database Propensity-Matched Cohort Study

Background Cardiovascular disease is a leading cause of non-cancer death among breast cancer survivors, who commonly receive 5 or more years of endocrine therapy. Aromatase inhibitors (AIs) deplete estrogen whereas tamoxifen retains partial estrogenic activity, yet whether they differ in real-world cardiovascular-kidney-metabolic (CKM) progression is undefined. Methods Using the TriNetX US Collaborative Network, we identified women with breast cancer initiating AIs or tamoxifen. Baseline CKM stage followed American Heart Association criteria (1-year pre-index window). For each transition, arms were matched 1:1 on age, race/ethnicity, body mass index, and cancer treatment, then followed 5 years (6,742, 12,854, 12,324, and 364 per arm). Cox models estimated hazard ratios (HRs); standardized mean differences were <0.10 except one. Results Versus tamoxifen, AIs showed higher early progression (stage 0-1 HR 1.22, 95% CI 1.13-1.32; stage 1-2 1.20, 1.14-1.27) but not stage 2-3 (1.05, 0.94-1.17). Ischemic heart disease rose across stages (HR 1.93, 1.35, 1.16, 2.03), as did cardiovascular disease (stage 0 CKM 4a 1.52, 4b 1.64; stage 2 heart failure 1.22, atrial fibrillation 1.19, stroke 1.15), metabolic outcomes (hyperlipidemia, type 2 diabetes, prediabetes), and chronic kidney disease. Restricted to ages 50-55, associations persisted or strengthened (stage 0 CKM 4a/4b 2.27 and 2.33; null stage 2-3 reached significance, 1.45, 1.01-2.09). Conclusion AIs were associated with greater early CKM progression and more cardiovascular events than tamoxifen. Because endocrine therapy selection differs by menopausal status and context, these associations likely reflect both treatment effects and differing source populations, not isolated causal effects, supporting cardiometabolic surveillance during endocrine therapy. Is this an encore abstract? No