Glucagon-like peptide−1 receptor agonist use and risk of postmastectomy lymphedema in breast cancer survivors: a multicenter real-world cohort study

PURPOSE: Postmastectomy lymphedema is a chronic survivorship complication after breast cancer treatment, particularly among patients exposed to axillary surgery. Obesity and metabolic inflammation are recognized contributors to lymphedema risk. This study evaluated whether glucagon-like peptide - 1 receptor agonist exposure was associated with lower incidence of coded postmastectomy lymphedema among breast cancer patients with mastectomy and/or axillary procedure exposure. METHODS: We performed a retrospective cohort study using deidentified electronic health record data from the TriNetX Research Network. Adult patients with breast cancer and coded mastectomy and/or axillary procedural exposure were stratified by GLP-1 receptor agonist exposure versus no exposure. One-to-one propensity score matching was used to balance measured baseline characteristics. The primary outcome was incident coded postmastectomy lymphedema syndrome. Outcomes were assessed from 1 to 650 days after the index event using risk estimates, Kaplan-Meier analysis, and Cox proportional hazards models. RESULTS: After propensity score matching, 61,630 patients were included, with 30,815 patients in each cohort. Coded postmastectomy lymphedema occurred in 258 of 29,259 GLP-1 receptor agonist users and 779 of 30,237 non-users, corresponding to incidence rates of 0.88% and 2.58%, respectively. GLP-1 receptor agonist exposure was associated with lower incidence of coded postmastectomy lymphedema in time-to-event analysis (hazard ratio 0.373, 95% CI 0.324-0.429; p < 0.001). The absolute risk difference was - 1.7%, with an estimated number needed to treat of 59. CONCLUSION: In this large real-world breast cancer surgical/procedural cohort, GLP-1 receptor agonist exposure was associated with lower incidence of coded postmastectomy lymphedema over 650 days of follow-up. These findings are hypothesis-generating and require prospective validation with systematic lymphedema assessment and detailed characterization of GLP-1 receptor agonist timing, duration, dose, and adherence.