Survival and Recurrence With GLP-1 Receptor Agonists in Breast Cancer

Importance: Patients with breast cancer (BC) with comorbid obesity or type 2 diabetes (T2D) experience poorer survival. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are approved to treat these comorbidities; however, their associations with BC survival and recurrence remain unclear. Objective: To evaluate the association between GLP-1 RA use and 10-year all-cause mortality and recurrence-free survival (RFS) over the 10-year follow-up period, as well as 5- and 10-year all-cause mortality and RFS probabilities among patients with BC. Design, Setting, and Participants: This retrospective cohort study used TriNetX US Collaborative Network data from women (≥18 years) with BC from 68 health care organizations who received a diagnosis between April 1, 2006, and April 1, 2023. Propensity score matching balanced characteristics. Data were analyzed between September 16 and October 3, 2025. Exposures: GLP-1 RA use (≥2 prescriptions) during the 6 months before and any time after the index diagnosis; nonuse (0 entries). Main Outcomes and Measures: The primary outcome was all-cause mortality, and the secondary outcome was RFS. Cox proportional hazards regression model-estimated hazard ratios (HRs) were restricted to 10 years. Kaplan-Meier estimators were used to calculate 5- and 10-year all-cause mortality and RFS probabilities. Prespecified subgroup (postmenopausal) and landmark (6- and 12-month) analyses were conducted. Results: The study comprised 841 831 eligible patients with BC (mean [SD] age, 69.1 [12.2] years). After exclusions and 1:1 propensity score matching, 3 cohorts were identified: 1610 patients for GLP-1 RA use vs nonuse (patients with obesity [body mass index ≥30]), 2323 patients for GLP-1 RA use vs insulin or metformin (patients with T2D), and 4052 patients for GLP-1 RA use vs sodium-glucose cotransporter 2 inhibitors (patients with T2D). Among patients with obesity, GLP-1 RAs were associated with lower hazard of all-cause mortality (HR, 0.35; 95% CI, 0.21-0.58; P < .001) and RFS (HR, 0.44; 95% CI, 0.30-0.64; P < .001) over a 10-year follow-up period. Among patients with T2D, GLP-1 RAs vs insulin or metformin were associated with lower hazard of all-cause mortality (HR, 0.09; 95% CI, 0.06-0.15; P < .001) and RFS (HR, 0.33; 95% CI, 0.21-0.50; P < .001). No significant differences were observed between GLP-1 RA and sodium-glucose cotransporter 2 inhibitor groups. Subgroup and landmark analyses yielded similar findings. Conclusions and Relevance: In this cohort study of patients with BC, findings suggested a potential association between GLP-1 RA use and improved outcomes among patients with BC who have obesity and related metabolic conditions. These findings support further evaluation of GLP-1 RA therapy in randomized clinical trials.