Abstract PS1-10-12: Impact of Glucagon-like peptide-1 receptor agonists Use on Survival and Metabolic Outcomes in Metastatic Estrogen Receptor Positive Breast Cancer: A Real-World Cohort Study

Abstract Background: Glucagon-like peptide-1 receptor agonists (GLP-1a), commonly used for type 2 diabetes and obesity, have shown potential anti-cancer effects in preclinical models. However, their impact on outcomes in patients with estrogen receptor-positive (ER+) metastatic breast cancer (MBC) remains unclear. This study evaluates the association between GLP-1a use and survival & metabolic outcomes in a real-world cohort of patients with ER+ MBC. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network. Two cohorts were defined: (1) ER+ MBC patients treated with GLP-1a (tirzepatide, dulaglutide, semaglutide, or liraglutide) and aromatase inhibitors (letrozole, anastrozole, or exemestane), excluding metformin users; and (2) ER+ MBC patients treated with aromatase inhibitors without GLP-1a or metformin. Cohorts were matched 1:1 using propensity scores based on demographics, comorbidities including type 2 diabetes mellitus and Obesity; and concurrent medications, including endocrine therapies (letrozole, anastrozole, exemestane) and other systemic treatments such as CDK4/6 inhibitors, mTOR inhibitors, and HER2-targeted agents. Kaplan-Meier survival analyses were performed for overall survival and adverse outcomes over a 2-year follow-up. Results: After propensity score matching, each cohort included 1,793 patients. GLP-1a use was associated with significantly improved 2-year overall survival (HR 0.612, 95% CI: 0.484-0.773, p