GLP-1 Receptor Agonists Show Modest Reduction in HR+ Breast Cancer Incidence

A real-world retrospective cohort analysis of more than 148,000 women presented during a poster session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting found that exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) was associated with a modest but statistically significant reduction in the incidence of hormone receptor (HR)–positive, HER2-negative breast cancer and meaningfully improved overall survival (OS) among non-diabetic women with body mass index (BMI) of 25 to 35 kg/m².¹

At the 36-month follow-up, incident HR-positive/HER2-negative breast cancer was observed in 0.29% of GLP-1 RA–exposed women vs 0.33% of women in the control arm, corresponding to an absolute difference of −0.04% (95% CI, −0.081% to −0.001%) and a risk ratio (RR) of 0.88 (95% CI, 0.77–0.99; P = .046). None of the secondary breast cancer subtypes reached statistical significance: HR-positive/HER2-positive (RR, 0.98; 95% CI, 0.86–1.12; P = .78), HR-negative/HER2-positive (RR, 0.83; 95% CI, 0.55–1.23; P = .35), and triple-negative breast cancer (TNBC; RR, 0.68; 95% CI, 0.41–1.12; P = .12).

Overall survival (OS) results were notable across all strata analyzed. In the full matched cohort of 148,709 women, GLP-1 RA exposure was associated with a 25% lower risk of death compared with controls (hazard ratio, 0.75; 95% CI, 0.65–0.86; P <.0001). When stratified by menopausal proxy, premenopausal-proxy women younger than 50 years (n = 57,132) experienced a 29% lower hazard of death with GLP-1 RA use (hazard ratio, 0.71; 95% CI, 0.58–0.86; P = .0004). Among the postmenopausal-proxy group of women aged 50 and older (n = 91,577), GLP-1 RA use remained independently associated with a statistically significant OS benefit (hazard ratio, 0.87; 95% CI, 0.81–0.94; P = .0003). Hazard ratios below 1.0 favored GLP-1 RA exposure.

Investigators from Roswell Park Comprehensive Cancer Center leveraged the TriNetX US Collaborative Network, a large federated real-world database, to assemble a propensity score–matched (PSM) cohort of female patients with a BMI of 25 to 35 kg/m² and no prior breast cancer or laboratory-defined diabetes (HbA1c <6.5%). Using PSM on age at index, BMI, metformin and statin exposure, BRCA mutation status, hormonal contraceptive use, parity, breastfeeding history, and smoking status, they identified two balanced cohorts: 74,354 GLP-1 RA–exposed women and 74,355 controls (total n = 148,709). Age below 50 vs 50 years or older served as proxies for premenopausal and postmenopausal status, respectively, with a sensitivity analysis conducted to assess age and menopausal confounding. Patients with HbA1c of 6.5% or higher or with prior breast cancer were excluded.

The primary end point was incident HR-positive/HER2-negative breast cancer, summarized as incidence proportion and risk reduction estimates. Secondary analyses assessed incidence of HR-positive/HER2-positive, HR-negative/HER2-positive, and triple-negative (HR-negative/HER2-negative) breast cancer subtypes. OS was evaluated using Kaplan–Meier methodology and Cox regression.

The authors concluded that, in this large real-world cohort of non-diabetic women with elevated BMI and no prior breast cancer, GLP-1 RA exposure was associated with both a modest reduction in incident HR-positive/HER2-negative breast cancer and meaningfully improved OS. They acknowledged limitations including the use of age-based menopausal proxies and the 36-month follow-up window, and called for prospective studies with standardized GLP-1 RA exposure definitions and longer observation periods to validate these findings.

Future investigation should also clarify whether the benefit is driven by direct antitumor effects of GLP-1 RAs or by indirect mechanisms mediated through weight loss and cardiometabolic risk reduction; they should also identify patient subgroups most likely to derive benefit. These results add to an expanding body of evidence linking GLP-1 RAs to favorable oncologic outcomes; a recently reported real-world analysis found that concurrent GLP-1 RA use was associated with improved long-term survival and reduced immune-related adverse events in patients treated with immune checkpoint inhibitors.²

References

1. Shah Z, Hundal J, Afridi SS, et al. GLP-1 therapy and hormone receptor–positive breast cancer risk and survival: A real-world analysis. J Clin Oncol. 2026;44(suppl 16):10548. doi:10.1200/JCO.2026.44.16_suppl.10548
2. Jajja S, Thukral J, Abdalla A, et al. The association of GLP-1 receptor agonist use with survival and immune-related adverse events in patients receiving immune checkpoint inhibitors: A multi-institutional real-world analysis. J Clin Oncol. 2026;44(suppl 16):11000. doi:10.1200/JCO.2026.44.16_suppl.11000.