A landmark study published June 2, 2026, in JCO Oncology Practice and simultaneously presented at the 2026 American Society of Clinical Oncology Annual Meeting by researchers at the University of Pennsylvania Perelman School of Medicine has produced findings that could reshape how America’s medical community thinks about GLP-1 receptor agonist drugs and how millions of women with obesity approach their own cancer risk.
The study, led by Dr. Elizabeth McDonald, a professor of radiology at Penn and practicing breast radiologist at Penn’s Abramson Cancer Center, found that women using GLP-1 medications were approximately 30% less likely to develop breast cancer than women who were not taking these drugs. The finding comes from an analysis of 111,646 women, the largest study of its kind, and the protective effect held even after rigorous statistical matching to control for confounding factors.
The scale and rigor of the Penn Medicine study are what elevate it above prior observational work in this area. Researchers used electronic health records from the University of Pennsylvania Health System, which includes both academic and community medical sites across Pennsylvania and New Jersey, to identify women aged 45 to 80 with a BMI of 25 or above who had undergone breast imaging between January 2022 and June 2025.
Of the 111,646 women in the full cohort, 15,264 (13.7%) had documented GLP-1 medication prescriptions, and 96,382 (86.3%) had no documented GLP-1 exposure. The researchers examined cancer incidence in both the full cohort and a matched cohort of 30,528 women, pairing each GLP-1 user one-to-one with a control patient matched on age, race, ethnicity, BMI, breast density, and diabetes status.
The result: 35.1% lower odds of breast cancer in the full analysis; 30.5% lower odds in the rigorously matched cohort.
Why the 30% Reduction Is Scientifically Credible
The breast cancer finding is consistent with what GLP-1 drugs do biologically. GLP-1 receptor agonists, the drug class that includes Ozempic (semaglutide), Wegovy (semaglutide), Mounjaro (tirzepatide), and Zepbound (tirzepatide), produce significant weight loss and improve key metabolic measures such as insulin sensitivity, inflammation levels, and sex hormone balance. Each of these changes is independently linked to lower breast cancer risk through well-established biological pathways.
Body fat is not just storage tissue; it is hormonally active. It converts androgens into estrogens through a process called aromatization. In postmenopausal women who are overweight or obese, fat tissue becomes the main source of circulating estrogen. Most breast cancers, about 70 to 75 percent, are estrogen receptor-positive, meaning they grow in response to estrogen. When weight is reduced, fat tissue decreases, aromatization declines, estrogen levels drop, and the growth stimulus for these cancers is reduced. This mechanism is widely accepted and helps explain why obesity increases breast cancer risk and why weight loss lowers it.
GLP-1 drugs also reduce chronic low-grade inflammation, measured through markers such as CRP, which can contribute to a tumor-friendly environment. In addition, they improve insulin resistance, lowering levels of insulin and IGF-1, both of which have been shown to directly promote breast cancer cell growth.
«While our study was observational and does not definitively confirm an association,» Dr. McDonald said, «it does add to the growing body of evidence suggesting that it’s worth investigating these weight-loss drugs as potential cancer prevention tools.»
The Philadelphia Context: Penn Medicine, Penn’s Abramson Center, and What This Means Locally
The Penn Medicine research carries particular significance in Philadelphia, where the study was conducted. The Penn Abramson Cancer Center, consistently ranked among the top cancer hospitals in the United States, is home to a major breast imaging and breast oncology program. The health system spans Pennsylvania and New Jersey, and the electronic health records used in the study reflect a real-world patient population in the greater Philadelphia region, including a wide range of body weight profiles, cancer risk factors, and GLP-1 prescribing patterns.
Philadelphia County has a breast cancer incidence rate above the national average, driven in part by higher obesity rates among women, especially in lower-income areas of North, West, and South Philadelphia. If GLP-1 drugs reduce breast cancer risk by 30% in overweight and obese women, the same group that accounts for much of the county’s burden, the public health impact could be significant. Access becomes the key issue. The women most likely to benefit are also those most likely to face insurance and cost barriers to GLP-1 treatment.
What Women Should Discuss with Their Doctors Now
The Penn Medicine study is observational — it does not prove causality and does not constitute a clinical recommendation to prescribe GLP-1 drugs for breast cancer prevention. Breast cancer prevention currently relies on lifestyle modification, screening adherence, chemoprevention with tamoxifen or aromatase inhibitors for high-risk individuals, and prophylactic surgical options for those with BRCA mutations.
What the study does justify is a conversation: women aged 45 to 80 who are overweight or obese, who are considering GLP-1 therapy for obesity or diabetes management, should ask their provider whether the breast cancer risk data adds weight to the clinical rationale for their treatment. For women who are already on GLP-1 medications, this study provides additional scientific support for the value of continued treatment. For oncologists, this data adds a new dimension to the patient conversation about weight management as cancer prevention — one with a specific drug class and a quantified risk reduction.
