The rapid adoption of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for obesity and diabetes has sparked interest in their potential effects on breast cancer risk and outcomes. At the 2026 ASCO Annual Meeting, investigators presented several observational studies examining the relationship between GLP-1 RA use and breast cancer, including analyses of prevention, detection, and outcomes among patients with established disease.^1,2,3

Although the studies add to a growing body of research in this area, experts emphasized that the evidence should be interpreted with caution.

How Do GLP-1 RAs Affect Prevention?

Because obesity is associated with both an increased risk of breast cancer and poorer outcomes after diagnosis, and risk-reducing therapies remain limited, investigators evaluated GLP-1 RAs as a potential alternative primary prevention strategy in high-risk women with obesity. In the real-world retrospective study presented at the meeting by lead author Nico-al Paolo Gotera, MPH, DO, Assistant Professor/Clinical, The University of Texas (UT) San Antonio, GLP-1 RA use was associated with an approximate 16% lower incidence of breast cancer than nonuse.¹

Using TriNetX, the investigators identified 80,480 adult women with obesity (body mass index [BMI] ≥ 30 kg/m²) and elevated breast cancer risk due to genetic, familial, or breast tissue–related factors. Women with a prior history of breast cancer or endocrine therapy use were excluded. After 1:1 propensity score matching, 40,240 GLP-1 RA users were compared with an equal number of nonusers.

With a median follow-up of approximately 2,700 days, the breast cancer incidence rate was 2.95% in users and 3.07% in nonusers (hazard ratio [HR] = 0.844; P < .001). The findings were consistent across multiple subgroups, Colton Jones, MD, a Hematology and Medical Oncology Fellow at UT San Antonio, told The ASCO Post at the meeting, with some of the strongest signals observed among women with a BMI greater than 40 kg/m² and those with a family history of breast cancer or benign mammary dysplasia. Statistically significant reductions in breast cancer risk were observed with multiple GLP-1 RAs, including semaglutide, tirzepatide, and dulaglutide. Of note, the association was seen among postmenopausal but not premenopausal women.

In the interview, Dr. Jones said investigators do not yet know why postmenopausal women appeared to derive a greater benefit and will need to review the data to determine whether this subgroup had a greater prevalence or severity of obesity.

Gastrointestinal adverse events were found to be significantly more common among users, whereas no significant association was observed with venous thromboembolism.

Summarizing the clinical implications of the study, Dr. Jones concluded, “Am I going to put my patient on a GLP-1 RA for breast cancer risk reduction? No, we need a prospective study to validate these findings.”

How Do GLP-1 RAs Affect Detection?

Taking a different approach to the question of breast cancer risk, Elizabeth McDonald, MD, PhD, Professor of Radiology at the University of Pennsylvania Perelman School of Medicine, and colleagues conducted a large retrospective observational cohort study examining whether GLP-1 RA use was associated with breast cancer detection among women undergoing breast imaging at a major academic center.²

The time is now to invest in a clinical trial to see if these drugs are causal for cancer prevention.

— ELIZABETH McDONALD, MD, PhD

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The investigators analyzed electronic health records from 111,646 women aged between 45 and 80 years with a BMI greater than 25 who underwent breast imaging (GLP-1 RA–unexposed, n = 96,382; GLP-1 RA–exposed, n = 15,264). Baseline characteristics were imbalanced between groups, with the GLP-1 RA–exposed cohort being younger and having higher rates of obesity and diabetes, as well as a greater comorbidity burden. To minimize confounding, the investigators used propensity score matching based on age, race, ethnicity, BMI, breast density, and diabetes status. The final analytic cohort included 15,264 matched pairs, with one control matched to each member of the exposed population.

Both the unmatched (1.6% vs 2.6%; odds ratio [OR] = 0.649; P < .0001) and matched (1.6% vs 2.3%; OR = 0.695; P < .0001) analyses showed that GLP-1 RA exposure before the exam date was associated with a significant reduction in breast cancer detection. Dr. McDonald described these findings during her presentation as a lower incidence of breast cancer, with an absolute risk reduction of 0.69% reported.

Dr. McDonald acknowledged during her presentation that observational data cannot establish causality. “We are seeing signals at this meeting in multiple cancers…. The time is now to invest in a clinical trial to see if these drugs are causal for cancer prevention,” she concluded. The ECOG-ACRIN Cancer Research Group plans to launch a randomized clinical trial, INSPIRE: INtegrated Strategies for Breast Cancer Prevention and Interception in Elevated-Risk Womento evaluate whether metabolic intervention can reduce risk in women with a history of breast cancer or those at elevated risk of developing the disease.

Although commending the researchers of the present study and others for their findings in the GLP-1–cancer space, invited discussant Rayjean J. Hung, PhD, FCAHS, Associate Director for Population Health and Professor at Sinai Health System and the University of Toronto, highlighted several considerations that may create or exaggerate apparent protective effects. These included selection bias related to GLP‑1 prescription, time-related biases, missing important risk factors, and, as Dr. McDonald noted, causal inference challenges. Building on Dr. McDonald’s sentiment, Dr. Hung noted that “[before randomized controlled trials], we need additional supportive evidence from mechanistic studies as well as real-world data accounting for some of the potential biases.”

Dr. Hung emphasized the need for more appropriate comparators (ie, active, comparator new user, cancer-risk–neutral); study design and analytical approaches that strengthen causal inference (eg, target trial emulation); negative control outcomes; and longer follow‑up.

How Do GLP-1 RAs Affect Outcomes?

“GLP-1 medications are now used by millions of Americans, so understanding their impact on cancer survivorship is increasingly important,” lead author Jasmine S. Sukumar, MD, Assistant Professor, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, told The ASCO Post. In a poster presented by Inimfon Jackson, MD, PhD, MPH, also an Assistant Professor in the department, investigators reported findings from one of the largest observational studies of real-world GLP-1 RA prescription patterns and associated mortality among patients with breast cancer.³

Using the Truven MarketScan database (now known as Merative MarketScan), the investigators identified 137,489 adult patients with invasive breast cancer who underwent definitive surgery, including 7,249 (5.3%) who received a GLP-1 RA for a median of 2.1 years and provided follow-up data for 32 months. A total of 53% underwent GLP-1 RA therapy concurrently with anticancer systemic therapy. GLP-1 RA use increased over time, with more than half of users initiating therapy after surgery. Semaglutide was the most prescribed agent and showed the greatest annual increase in use after 2018.

Most GLP-1 RA users had type 2 diabetes, a quarter had a Charlson Comorbidity Index score of at least 3, and nearly all with available weight data were overweight or obese. After propensity score matching based on several clinical prognostic factors (n = 7,239 per group), use appeared to be associated with significantly higher 5-year overall survival rates compared with nonuse (95.8% vs 91.3%; adjusted HR = 0.48; P < .0001). Dr. Sukumar said that “this could reflect improvements in metabolic and cardiovascular health, effects on treatment tolerance, or potentially direct biologic anticancer effects, but the underlying mechanisms have not yet been defined.”

“Our findings provide an encouraging signal, but they do not establish causality. While these agents have well-established benefits for diabetes, obesity, and metabolic health, whether they directly improve cancer health outcomes remains unknown and will require clinical trials,” she concluded in her interview. “In the meantime, treatment decisions across the cancer care trajectory should remain individualized, with healthy diet and regular exercise continuing to play a central role in survivorship care.”

DISCLOSURE: Dr. Gotera, Dr. Jones, Dr. McDonald, Dr. Hung, and Dr. Jackson reported no conflicts of interest. Dr. Sukumar has received honoraria from Amplity; has held a consulting or advisory role with NEJM Group; and has received research funding from The Bristol Myers Squibb Foundation.

REFERENCES

1. Gotera NP, Jones C, Gelfond J, et al: GLP-1 receptor agonists for primary prevention of breast cancer in high-risk women: A real-world analysis of efficacy and safety. 2026 ASCO Annual Meeting. Abstract 10520. Presented June 1, 2026.

2. McDonald ES, Gillis L, Gabriel P, et al: Association of GLP-1 agonists with breast cancer incidence in women. 2026 ASCO Annual Meeting. Abstract 10506. Presented June 2, 2026.

3. Sukumar JS, Niu J, Jackson I, et al: Real-world treatment patterns and mortality associated with GLP1-RAs in breast cancer patients. 2026 ASCO Annual Meeting. Abstract 629. Presented June 1, 2026.

MORE INFORMATION

For more on the study of GLP-1 RAs and breast cancer incidence (Abstract 10506), see a video with Elizabeth McDonald, MD, PhD, on The ASCO Post Newsreels at ascopost.com/videos.