GLP-1 Receptor Agonists versus Bariatric Surgery in Breast Cancer: A Comparative Study of Oncologic Outcomes

Obesity contributes to chronic inflammation and estrogen dysregulation, mechanisms linked to increased breast cancer (BC) risk and recurrence, particularly in postmenopausal women. Bariatric surgery and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective weight-loss interventions, but their comparative impact on BC outcomes remains unclear. This study compared long-term overall survival (OS) and locoregional recurrence (LRR) among postmenopausal BC patients with obesity treated with GLP-1RAs, bariatric surgery, or both.

Using the TriNetX Network, a real-world federated research database of de-identified electronic records from multiple health care organizations, we identified women aged ≥50 years with BMI ≥30 kg/m² and stage 0-III BC. Study 1 compared patients who initiated GLP-1RA therapy ≥6 months after BC diagnosis with those who underwent bariatric surgery during the same interval. Study 2 compared patients who received both bariatric surgery and GLP-1RA therapy with those who underwent surgery alone. Propensity score matching (1:1) was performed for age, BMI, tumor stage, receptor status, adjuvant therapy, other cancers, and comorbidities. Outcomes included OS and LRR, assessed from 30 days to 10 years after the index event (bariatric surgery or GLP-1RA initiation). Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards models.

In Study 1, 22,532 GLP-1RA users and 3468 bariatric surgery patients were identified; 3438 were matched in each cohort. 10-year OS was similar (87% vs. 83%), yet GLP-1RA users experienced significantly lower instantaneous mortality risk (HR 0.57, 95% CI: 0.45-0.73), indicating fewer or delayed deaths over time. LRR occurred in 1.8% vs. 4.7% (HR 0.52, 95% CI: 0.39-0.70), also favoring GLP-1RA therapy.In Study 2, 1220 patients underwent both bariatric surgery and GLP-1RA therapy and 3468 underwent surgery alone; 1129 were matched per group. The combination group showed higher OS (91% vs. 80%; HR 0.44, 95% CI: 0.29-0.67) and lower LRR (2.5% vs. 5.8%; HR 0.52, 95% CI: 0.33-0.81).

Among postmenopausal women with obesity and stage 0-III BC, GLP-1RA therapy was associated with improved OS and lower LRR compared with bariatric surgery alone. Combination therapy achieved the most favorable oncologic outcomes, suggesting a potential synergistic effect. The advantage observed with GLP-1RAs may reflect oncologic effects beyond weight loss, potentially through anti-inflammatory, insulin-modulating, or other metabolic pathways. These findings support further investigation into the underlying biological mechanisms and potential role of GLP-1RAs in oncology.