A real-world analysis on the management of post-mastectomy lymphedema in breast cancer patients: The therapeutic promise of glucagon-like peptide-1 receptor agonist.

e12695 Background: Post mastectomy lymphedema syndrome (PMLS) is an established complication of mastectomy, and the risk is further exacerbated by obesity and insulin resistance. Glucagon-like-peptide 1 receptor agonists (GLP-1RAs) are known to reduce body mass index (BMI) and inflammation while improving insulin sensitivity. However, data on the management of PMLS with GLP-1RA in breast cancer (BC) patients is limited to case reports and clinical observations. To address this evidence gap, we conducted the first retrospective multicenter, real-world analysis to assess the efficacy and safety of GLP-1RA for the management of PMLS in BC patients. Methods: All BC patients aged 18-90 years with a diagnosis of PMLS between January 1, 2000, and January 1, 2025, were identified in the TriNet X database (150 million patients across 108 healthcare organizations). BC patients on GLP-1RA therapy of ≥ 2 months (cohort A) were matched to non-users (cohort B) using propensity score matching (1:1). The primary endpoint was the incidence of lymphedema-associated complications (lymphangitis, cellulitis, skin ulcer/breakdown, upper limb pain). Secondary endpoints included utilization of diagnostics (lymphoscintigraphy), procedures (manual lymphatic drainage), and pain medication utilization. Patients with outcomes before the study window were excluded. Cox proportional hazards and multivariate logistic regression analysis were performed to assess if there was a significant reduction in the primary and secondary endpoints. Subgroup analysis was performed. Results: Among 4,580 matched BC patients, 2,290 were assigned to each cohort (demographics were similar: mean age of 61 vs 61 years, White 69% vs 71%, Black 21% vs 20%; however, mean BMI was higher in the GLP-1RA cohort: 36 vs 31). GLP-1RA use was associated with a 59% reduction in lymphangitis [HR: 0.41 (0.22–0.76)], a 53% reduction in manual lymphatic drainage [HR: 0.47 (0.39–0.56)], and a 61% reduction in lymphoscintigraphy utilization [HR: 0.38 (0.23–0.64)]. No significant reductions were observed in cellulitis, skin breakdown, or pain medication utilization. Notably, subgroup analyses of non-diabetic patients and those with BMI < 29 demonstrated consistent therapeutic benefits. Conclusions: GLP-1RA use was associated with a significant reduction in lymphangitis and healthcare utilization for PMLS. This protective signal remained consistent across non-obese and non-diabetic subgroups, suggesting a disease-modifying effect potentially driven by improved lymphatic flow and reduced inflammation. These findings warrant prospective validation as they have important implications for clinical practice.