E. Robert McDonald, Laura Gillis, Peter Gabriel, Kham Xapakdy, Anthony Young, Abigail Doucette, Mitchell D. Schnall, John B. Buse, Etta D. Pisano
PURPOSE Excess weight is a key modifiable risk factor for breast cancer. Glucagon-like peptide-1 receptor agonists (GLP-1) promote weight loss and improve metabolic health, but their effect on breast cancer risk remains unclear. METHODS We conducted a retrospective cohort study from January 1, 2022, to June 30, 2025, using electronic health records. We identified 217,624 unique women who underwent breast imaging; restricting to ages 45-80 years with a BMI ≥25 and a documented imaging outcome (n = 111,646; median age 61 years). The primary outcome was breast cancer detection. GLP-1 use was defined as a first prescription before the examination date and assessed in relation to race, ethnicity, age, and type 2 diabetes. To address potential confounding between these covariates and GLP-1 exposure, we performed one-to-one, case-control matching using propensity scores on the basis of age, race, ethnicity, highest BMI, breast density, and history of type 2 diabetes. The propensity matching to the GLP-1 use group was performed using the greedy nearest neighbor approach. RESULTS GLP-1 exposure was associated with a lower incidence of breast cancer (odds ratio [OR], 0.649 [95% CI, 0.569 to 0.741]; P < .0001). In the matched logistic regression (30,528 observations; 600 cancer cases), GLP-1 exposure was associated with a lower breast cancer incidence (OR, 0.695 [95% CI, 0.590 to 0.819]; P < .0001). CONCLUSION In this large observational study of women undergoing breast imaging at a major academic center and affiliated sites, GLP-1 treatment was associated with a lower incidence of breast cancer, independent of age, race, ethnicity, BMI, breast density, and diabetes. The findings support the need for prospective trials investigating GLP-1 agonists for breast cancer prevention.