CHICAGO — A study of women undergoing breast imaging showed a significantly lower incidence of breast cancer in those who had a history of treatment with GLP-1 agonists.
Involving more than 30,000 women, the study showed an overall breast cancer rate of 1.97%, including 1.62% in patients who received GLP-1 agonists for overweight or obesity and 2.31% in those who did not. The difference represented a 30% lower risk of breast cancer in the GLP-1 group.
The findings, combined with multiple other studies, have provided impetus for a prospective clinical trial of GLP-1 drugs to prevent breast cancer, reported Elizabeth S. McDonald, MD, PhD, of Penn Medicine and Abramson Cancer Center in Philadelphia, at the American Society of Clinical Oncology (ASCO) meeting.
“Observational data cannot establish a causal relationship,” said McDonald. “We are seeing signals at this meeting in multiple cancers — colon, lung, liver, leukemia, endometrial, multiple myeloma — for decreased progression to metastatic disease, decreased recurrence, decreased incidence, and increased survival. The time is now to invest in a clinical trial to see if these drugs are causal for cancer prevention.”
“Since one in eight women get breast cancer, breast is the ideal tumor type around which to build a prospective clinical trial, due to the high number of events, so we are poised to launch a large-scale clinical trial to test the cancer preventative impact of GLP-1 agonists within the next few months,” she said.
The trial will involve women with a family history of breast cancer or otherwise at high risk for the disease, she added. The study will examine GLP-1 agonists in primary and secondary breast cancer prevention, as well as cardiovascular prevention, in overweight, non-obese women.
Among the ASCO studies referenced by McDonald, a retrospective cohort analysis showed a 51% reduction in the risk of acute myelogenous leukemia (AML) in high-risk patients who received GLP-1 agonists for overweight or obesity. In patients with a history of treatment with chemotherapy, GLP-1 use was associated with a 74% lower risk of AML and reductions of 71% and 50%, respectively, for acute lymphoblastic leukemia (ALL) and chronic myelogenous leukemia (CML), as reported by Colton Jones, MD, of UT Health San Antonio.
Breast Cancer Study
McDonald reported findings from a retrospective cohort study involving 111,646 women ages 45-80 (median 61), with overweight or obesity (body mass index [BMI] ≥25), who underwent breast imaging from Jan. 1, 2022 through June 30, 2025. Data analysis included 15,264 patients who had at least one prescription for a GLP-1 agonist and 96,382 patients with no history of exposure to a GLP-1 agonist.
Baseline characteristics showed the GLP-1-exposed group had higher rates of class 2-3 obesity and type 2 diabetes (66% vs 28% and 53% vs 18%). The GLP-1 group also had more patients with high/very high Charlson comorbidity risk scores (41% vs 24%). Radiographic results showed a significantly higher rate of breast cancer in women with no GLP-1 exposure (2.6% vs 1.6%, OR 0.649, 95% CI 0.569-0.741, P<0.0001), as well as a history of breast cancer (9.2% vs 5.9%).
The primary analysis included propensity-matched cohorts of 15,264 patients each. The lower rate of imaging-detected breast cancer among GLP-1-exposed women in the overall population carried over in the matched analysis, with a similar odds ratio (OR 0.695, 95% CI 0.590-0.819, P<0.0001).
Reduced Leukemia Risk
Currently, no FDA-approved therapies exist for leukemia risk reduction, Jones noted in his introductory comments. GLP-1 agonists target metabolic and epigenetic pathways associated with leukemia pathogenesis, and studies have shown the drugs reduce pathway signaling in leukemia cells.
To add real-world data to the evidence base, investigators queried the TriNetX database and produced two propensity-matched cohorts of 313,099 patients, one with a history of GLP-1 exposure and the other without. Covering the years 2000 to 2025, the two cohorts were matched for demographics, BMI, HbA1c, and comorbidities. The two groups had a median age of about 44 and white patients and women each accounted for 71%.
The analysis yielded a hazard ratio of 0.49 for AML in favor of GLP-1 exposure (95% CI 0.34-0.70, P<0.0001). The outcome was similar across age groups, BMI categories, and diabetes status. In an analysis involving patients with a history of chemotherapy exposure (a risk for secondary malignancy), the hazard ratio decreased to 0.26 (95% CI 0.17-0.40, P<0.0001).
Subsequent analyses showed GLP-1 exposure associated with a 32% reduction in the hazard for ALL (95% CI 0.43-1.07, P=0.090), increasing to 71% in the chemotherapy-exposed subgroup (95% CI 0.18-0.47, P<0.0001). For CML risk, the overall analysis showed no significant association with GLP-1 exposure (HR 0.91), but patients with a history of chemotherapy exposure had a statistically significant 50% reduction in the hazard (95% CI 0.30-0.82, P=0.005). GLP-1 exposure was not associated with a lower risk of chronic lymphoblastic leukemia in the overall analysis or chemotherapy subgroup.
The lower risk associated with GLP-1 use came at a price of more toxicity at the starting dose, Jones noted, including significantly higher rates of nausea and vomiting, abdominal pain, diarrhea, and constipation.
