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GLP-1 Receptor Agonists vs Bariatric Surgery in Breast Cancer: A Comparative Study of Oncologic Outcomes
*Jennifer Den2, *Raj Vaghjiani
1, Vicki S. Klimberg
11Surgery, The University of Texas Medical Branch at Galveston, Galveston, Texas; 2Surgery, UTMB, Galveston, Texas
BackgroundObesity 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 local recurrence (LR) among postmenopausal obese BC patients treated with GLP-1RAs, bariatric surgery, or both.
MethodsA retrospective study was conducted using the TriNetX database to identify 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 LR, 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.
ResultsIn Study 1, 22,532 GLP-1RA users and 3,468 bariatric surgery patients were identified; 3,438 were matched in each cohort. Ten-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. LR occurred in 1.8% vs 4.7% (HR 0.52, 95% CI 0.39-0.70), also favoring GLP-1RA therapy.
In Study 2, 1,220 patients underwent both bariatric surgery and GLP-1RA therapy, and 3,468 underwent surgery alone; 1,129 were matched per group. The combination group showed higher OS (91% vs 80%; HR 0.44, 95% CI 0.29-0.67) and lower LR (2.5% vs 5.8%; HR 0.52, 95% CI 0.33-0.81).
ConclusionsAmong postmenopausal women with obesity and stage 0-III BC, GLP-1RA therapy was associated with improved OS and lower LR compared to 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 highlight the need for further investigation into the underlying biological mechanisms and the potential role of GLP-1RAs as adjuvant therapy.
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