10506 Background: Excess weight is a key modifiable risk factor for breast cancer. Glucagon-like peptide-1 receptor agonists (GLP-1) promote weight loss and improve markers of metabolic health. However, the effect of GLP-1 on breast cancer risk among women eligible for breast cancer screening remains unclear. Methods: We conducted a retrospective, time-dependent cohort study from January 1, 2022, to June 30, 2025, using electronic health records. We identified 217,025 unique patients who underwent breast imaging, restricting the sample to women aged 45 to 80 years with a BMI greater than 25 and a documented imaging outcome (n=94,827; median age 61). The primary outcome was breast cancer detection. GLP-1 use was defined as a first prescription prior to the exam 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 based on age, race, ethnicity, highest BMI, breast density, and type 2 diabetes diagnosis. Results: Among 94,827 women, 2,314 (2.4%) were diagnosed with breast cancer during the study period, while 92,513 (97.6%) were not. Of the total, 15,107 (15.9%) had GLP-1 exposure, and 79,720 (84.1%) did not. Among those exposed to GLP-1, 249 (1.65%) developed breast cancer, while 14,858 (98.4%) did not. Among women without exposure to GLP-1, there were 2065 (2.6%) women with breast cancer and 77,655 (97.4%) of women without breast cancer. GLP-1 exposure was associated with a lower incidence of breast cancer (OR 0.630 (0.552, 0.720 ); p<0.0001). In the matched logistic regression analysis (30,214 observations; 581 cancer cases), GLP-1 exposure prior to the exam date was associated with a lower incidence of breast cancer (OR 0.746, 95% CI: 0.632–0.880; p<0.0005). Conclusions: In this large observational study of women undergoing breast imaging at a major academic center, GLP-1 treatment was associated with a significantly lower incidence of breast cancer after accounting for age, race, ethnicity, BMI, breast density, and type 2 diabetes status. These findings support the need for prospective trials investigating incretin medications for breast cancer prevention. Matched case-control contingency table for GLP-1 exposure prior to exam date and breast cancer. No cancer Total GLP-1 249 (1.65%) 14858 (98.35%) 15107 No GLP-1 332 (2.20%) 14775 (97.80%) 15107 Total 581 (1.92%) 29633 (98.08%) 30214
McDonald et al. (Wed,) studied this question.