240P Impact of the RSClin tool on chemotherapy (CT) recommendations in node-negative hormone receptor-positive (HR+), HER2-negative (HER2-) early breast cancer (BC): A real-world analysis

contributors to breast cancer development and prognosis.We therefore evaluated whether GLP-1 exposure prior to diagnosis is associated with breast cancer outcomes in a large real-world population. Methods:We performed a retrospective TriNetX cohort study of adults with newly diagnosed breast cancer, classified by GLP-1 receptor agonist exposure within five years prior to diagnosis.After 1:1 propensity score matching, all-cause mortality from diagnosis was assessed using odds ratios and Kaplan-Meier and Cox survival analyses.Results: After matching, 32,852 patients were included (16,426 per group).Prior GLP-1 exposure was associated with lower cumulative all-cause mortality following breast cancer diagnosis (OR 0.91, 95% CI 0.84-0.99;p=0.028), with significant separation of Kaplan-Meier survival curves (log-rank p<0.001;HR 0.81, 95% CI 0.75-0.88),although median survival was not reached in either group.At three years, mortality occurred in 5.0% of GLP-1-exposed patients versus 5.9% of nonexposed patients (OR 0.85, 95% CI 0.77-0.93;p=0.001), with a significantly reduced hazard of death (HR 0.77, 95% CI 0.70-0.84).At five years, cumulative mortality remained lower among GLP-1-exposed patients (6.9% vs 7.5%; OR 0.88, 95% CI 0.81-0.96;p=0.005).In the hormone receptor-positive (HR+) subgroup, prior GLP-1 exposure was associated with a greater reduction in mortality (OR 0.82, 95% CI 0.70-0.95) and a 26% lower hazard of death (HR 0.74, 95% CI 0.64-0.86;p=0.009). Conclusions:Pre-diagnosis GLP-1 receptor agonist exposure was associated with lower all-cause mortality following breast cancer diagnosis in this large real-world cohort.The association was strongest in hormone receptor-positive disease, a subtype closely linked to metabolic and inflammatory pathways.These findings support the hypothesis that metabolic modulation through weight and insulin resistance reduction may influence breast cancer survival and warrant further prospective investigation.