Abstract PS5-11-16: Impact of GLP-1 Receptor Agonist Exposure on the Long-Term Survival in Breast Cancer Patients

Abstract Background: Obesity is a known risk factor for the development of breast cancer, and weight gain after treatment of early-stage disease is associated with worse outcomes, including cancer-specific outcomes. Some of the proposed mechanisms for adverse outcomes in obese patients include the pro-tumorigenic environment from circulating cytokines, impaired adipokine function, and differential efficacy of systemic treatments. Weight reduction strategies in breast cancer patients have largely been unsuccessful. The GLP-1 receptor agonists (GLP-1RAs) have the potential to produce meaningful weight loss; however, the impact of these agents on breast cancer outcomes has not been well characterized. Methods: Diabetic patients with invasive breast cancer diagnosed between 2009 and 2024 were identified using the City of Hope tumor registry through an IRB approved protocol. Patients were divided into those who had been treated with GLP-1RA after breast cancer diagnosis (cases, n = 232) versus those who had not (controls, n = 722). The groups were compared using t-tests for continuous variables and chi-square tests for categorical variables. Multivariable logistic regression models were used to examine differences between cases and controls, while multivariable Cox proportional hazards models were used to examine differences in overall mortality. Included in the multivariable models were the following covariates: diagnosis year, age group (55 vs. 55+), race, ethnicity, BMI, tumor stage, tumor grade, ER/PR status, HER2 status, receipt of surgical resection, receipt of hormone therapy (AI and/or SERMs), receipt of chemotherapy, and receipt of radiation therapy. Results: The cases were younger (57 years vs. 62 years, p 0.001) and had higher BMIs (33 vs. 29, p 0.001) at diagnosis than controls. Patients were similar across case/control status for the following covariates: year at diagnosis, tumor stage, tumor grade, ER/PR status, and Her2 status. The use of hormone therapy was also similar across groups. Using a multivariable logistic regression model, cases were found to have significantly lower risk of death than controls (OR = 0.33, CI 0.18 - 0.62, p 0.001). Similarly, a multivariate Cox proportional hazards model showed a significantly lower risk of mortality in cases than controls (HR = 0.34, CI 0.19 - 0.60, p 0.001). After stratifying for age group, tumor stage, ER/PR status, and Her2 status, mortality risk remained lower for cases who were aged 55+, stage II, ER/PR positive, and Her2 negative (all p0.05) compared to controls. The remaining subgroups also showed lower risk of mortality in cases, however, sample sizes were too small to reach statistical significance. Conclusion: Our institutional tumor registry data suggest an advantage for the use of GLP-1RA in women with breast cancer who also have diabetes. Well-designed controlled trials are needed to validate these findings. Importantly, we did not find any adverse effect from the use of GLP-1RA in our diabetic breast cancer population. Citation Format: R. Nelson, Y. Lai, S. Kil, H. Lee, J. Mortimer, P. H. Wang. Impact of GLP-1 Receptor Agonist Exposure on the Long-Term Survival in Breast Cancer Patients 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 PS5-11-16.