Abstract Background: Ductal carcinoma in situ (DCIS) is a non-invasive breast neoplasm that carries a risk of progression to invasive and metastatic disease. The potential impact of glucagon-like peptide-1 (GLP-1) receptor agonists, commonly used in diabetes management, on breast cancer outcomes in DCIS patients receiving hormonal therapy remains unclear. Methods: Using the TriNetX Research Network, we conducted a retrospective cohort study comparing patients with DCIS on hormonal therapy with (Cohort 1, n=3,049) and without (Cohort 2, n=3,049) concomitant GLP-1 agonist use. Cohorts were propensity score matched on demographic, clinical, and laboratory parameters. The primary outcomes were the incidence of invasive and metastatic breast cancer, overall survival, and progression to stage IV disease over a 5-year period. Risk estimates, survival probability, hazard ratios (HR), and associated 95% confidence intervals (CIs) were calculated. Results: GLP-1 agonist use was associated with a significantly reduced risk of invasive and metastatic breast cancer (risk 4.1% vs 10.8%; risk difference -6.6%, 95% CI -7.9% to -5.3%; HR 0.36, 95% CI 0.29-0.44, p0.001). Similarly, the risk of progression to stage IV disease was lower in the GLP-1 cohort (3.8% vs 10.6%; risk difference -6.7%, 95% CI -8.0% to -5.4%; HR 0.34, 95% CI 0.27-0.42, p0.001). Overall survival was higher among GLP-1 users, with a 5-year survival probability of 93.5% compared to 85.7% in non-users (HR 0.37, 95% CI 0.29-0.47, p0.001). Conclusions: In this large, real-world cohort, GLP-1 receptor agonist use was associated with significantly reduced risk of invasive/metastatic breast cancer and improved overall survival in patients with DCIS on hormonal therapy. These findings warrant further investigation through prospective trials to elucidate potential biological mechanisms and therapeutic implications. Citation Format: A. Y. Khan, F. A. Khan, M. Khan, S. U. Safi, D. Safi. Glp-1 receptor agonists are associated with improved breast cancer outcomes in dcis patients on hormonal therapy: a real-world cohort study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD8-08.
Khan et al. (Tue,) studied this question.