Journal of surgical oncology · 2026
The Effect of Glucagon-Like Peptide 1 Receptor Agonists on Peri- and Postmenopausal Breast Cancer Outcomes.
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Den Jennifer, Nelson Nicole, Vaghjiani Raj, Suzanne Klimberg V
Аннотация
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/m2. 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/m2, 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.
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/m2. 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/m2, 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.