A trio of large observational studies reported at the San Antonio Breast Cancer Symposium (SABCS) 2025 suggest that GLP-1 receptor agonists may improve outcomes in some women with breast cancer.

Two studies reported an overall survival benefit of GLP-1 use in certain patients with breast cancer, including those with ductal carcinoma in situ (DCIS) and invasive hormone receptor (HR)-positive nonmetastatic disease, and a third found improvements in a range of toxicities among patients receiving chemotherapy.

These studies, presented during a poster session, add to other emerging research indicating that GLP-1 drugs could have implications across the breast cancer trajectory, including prevention, active therapy, and posttreatment survivorship, explained study discussant Jasmine S. Sukumar, MD, with University of Texas MD Anderson Cancer Center in Houston.

One study focused on the effects of GLP-1 use among patients with HR-positive breast cancer of any stage and obesity who were on adjuvant endocrine therapy.

In a propensity-matched cohort of 8784 GLP-1 users and 8784 nonusers, GLP-1 use was associated with a significant improvement in all-cause mortality after a median follow-up of nearly 6 years (hazard ratio [HR], 0.54; P = .019).

This mortality benefit was consistent across multiple subgroups, including age, BMI, diabetes status, endocrine therapy type, and GLP-1 agent, with semaglutide and tirzepatide having the most pronounced benefit, lead author Colton Jones, MD, with UT Health Science Center at San Antonio, told attendees.

Jones noted, however, that GLP-1s appeared to significantly worsen endocrine therapy side effects, most notably joint pain, depression, hot flashes, osteoporosis, and endometrial cancer risk. The endometrial cancer risk finding requires further study, he said.

Another analysis suggested the opposite for chemotherapy-related side effects — that GLP-1 agonists may attenuate a range of adverse events in patients with breast cancer.

In this retrospective study, which included propensity-matched GLP-1 users (n = 5685) and nonusers (n = 5685) receiving chemotherapy to treat breast cancer, GLP-1 use was associated with significant reductions in hematologic, gastrointestinal, cardiovascular, and systemic toxicities after multivariate adjustment (P < .0001 for all).

Compared to nonusers, GLP-1 users had significantly lower risks for anemia (relative risk [RR], 0.617), venous thromboembolism (RR, 0.592), neutropenia (RR, 0.478), thrombocytopenia (RR, 0.587), sepsis (RR, 0.679), nausea/vomiting (RR, 0.711), fatigue (RR, 0.755), cardiomyopathy (RR, 0.651), and neuropathy (RR, 0.717).

It’s unclear why GLP-1s may worsen endocrine therapy side effects while easing chemotherapy side effects, and this difference should be studied further, first author Elvis Obomanu, MBBS, with Jefferson Einstein Philadelphia Hospital in Philadelphia, and colleagues said.

The third study, presented by Danish Safi, MD, with West Virginia University in Morgantown, West Virginia, provided a “real-world signal” that GLP-1 receptor agonists may improve outcomes in women with DCIS.

In this propensity-matched cohort of more than 6000 women with DCIS on hormonal therapy, GLP-1 agonist use was associated with a significantly reduced risk for invasive or metastatic breast cancer progression compared with nonuse (4.1% vs 10.8%; risk difference, -6.6%; HR, 0.36; P < .001).

Overall survival at 5 years was also higher among GLP-1 users than among nonusers (93.5% vs 85.7%; HR, 0.37; P < .001).

The findings highlight a “potential dual metabolic and oncologic benefit” of GLP-1 agonists and “support incorporating metabolic interventions into breast cancer follow-up,” Safi said.

However, the associations should be viewed as “hypothesis-generating” because missing DCIS-specific pathology and treatment variables could introduce confounding, Safi explained.

Study discussant Sukumar congratulated the researchers for their “interesting work on the timely topic of obesity, GLP-1 therapies, and breast cancer” but agreed that the data at this point should be viewed as “hypothesis-generating.” Sukumar noted that disparities in uptake and gaps in equitable access are already evident and would need to be addressed if GLP-1 use expands in patients with cancer.

Sukumar also highlighted several key unanswered questions in this space, such as whether potential survival benefits with GLP-1s in breast cancer are mediated indirectly through metabolic effects or through direct antitumor mechanisms; how GLP-1s influence recurrence risk by subtype and stage; what the interaction between GLP-1s and immunotherapy is; and how dosing, adherence, and drug type matter.

“It’s really prime time for prospective, well-designed, controlled trials so we can more formally answer these cancer-specific endpoints,” Sukumar concluded.

This research had no commercial funding. Jones , Obomanu, and Safi had no disclosures. Sukumar received grant/research support from the American Society of Clinical Oncology, the Breast Cancer Research Foundation, and Bristol Myers Squibb Foundation and honoraria from Amplity Health and the NEJM Group.