The Effect of Glucagon‐Like Peptide 1 Receptor Agonists on Peri‐ and Postmenopausal Breast Cancer Outcomes
Jennifer Den, Nicole Nelson, Raj Vaghjiani, V. Suzanne KlimbergABSTRACT
Introduction
Studies have shown that obesity increases the risk of postmenopausal breast cancer (BC) by 30%–60% and is associated with poorer outcomes. This is believed to be related to continued exposure to estrogen and prolonged inflammation. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have been suggested to significantly lower the risk of several obesity‐associated cancers (OACs). We hypothesize that GLP‐1RAs can improve outcomes in peri‐ and postmenopausal BC patients with obesity.
Methods
We conducted a retrospective cohort study using the TriNetX database to compare the outcomes of female BC patients ≥ 45 years old with a BMI of ≥ 35 kg/m 2 . We created two cohorts: those who took GLP‐1RAs with a Stage I‐III BC diagnosis and those who never had exposure to GLP‐1RAs. Patients' propensity score was matched based on age, BMI, diabetes, socioeconomic status, and genetic carrier status. Our outcomes of interest were 10‐year overall survival (OS) and local recurrence (LR).
Results
We identified 10 498 patients who used GLP‐1RAs and 93 174 patients who did not. After matching, 19 348 patients were identified, with 9674 per cohort. 10‐year OS with the Kaplan‐Meier analysis was significantly greater in patients on GLP‐1RAs (79%) compared to those not on GLP‐1RAs (71%), log‐rank test p < 0.0001. The HR for OS was 0.54, 95% CI (0.49–0.60). The risk of LR was significantly lower (HR 0.481, 95% CI (0.425–0.546)).
Conclusions
Among peri‐ and postmenopausal breast cancer patients with BMI ≥ 35 kg/m 2 , GLP‐1RA use after diagnosis was associated with improved 10‐year OS and lower LR. These findings are hypothesis‐generating but suggest a potential therapeutic role for GLP‐1RAs, warranting prospective investigation in this high‐risk population.