- A retrospective study suggests that GLP-1 use amongst those with overweight or obesity was linked to a substantially lower risk of breast cancer.
- The association remained significant after matching for key risk factors, such as age, race, ethnicity, BMI, breast density, and diabetes status, suggesting the findings were not solely due to differences between groups.
- Researchers suggest multiple biological mechanisms may be involved, including reducing inflammation and altering pathways that may play a role in cancer development.
- However, the study cannot determine whether GLP-1 drugs directly prevent breast cancer, but supports further clinical research to investigate whether they could serve as a breast cancer prevention strategy.
Overweight and obesity are well-established
Obesity is also associated with chronic low-grade inflammation, insulin resistance, and elevated levels of insulin-like growth factors, all of which can promote cancer development and progression. Studies have also shown that females with obesity may have a higher risk of breast cancer recurrence and poorer survival outcomes.
Maintaining a
Now, a large observational study adds to this evidence, suggesting that women taking GLP-1 drugs were significantly less likely to develop breast cancer than those who were not prescribed the medications.
The findings, presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and published simultaneously in JCO Oncology Practice, suggest those taking GLP-1 medications had approximately 30% lower odds of developing breast cancer compared with non-users.
The results have prompted a clinical trial to determine whether the association reflects a true protective effect.
The researchers analyzed electronic health records from 111,646 females ages 45 to 80 years, who had a body mass index (BMI) of 25 or higher and underwent breast imaging within the Penn Medicine health system between January 2022 and June 2025.
Among the participants, 15,264 females (13.7%) had documented prescriptions for GLP-1 medications and 96,382 women (86.3%) had no documented exposure to GLP-1 drugs.
The research team examined rates of newly diagnosed breast cancer in two groups: the full study population and a smaller matched cohort of 30,528 women. In the matched analysis, each GLP-1 user was paired with a non-user who had similar characteristics, including age, race, ethnicity, BMI, breast density, and diabetes status.
Across both analyses, GLP-1 use was associated with significantly lower breast cancer incidence. In the full cohort, GLP-1 users had 35.1% lower odds of developing breast cancer. In the matched cohort, the reduction was 30.5%.
The consistency of the findings across both analyses strengthens confidence that the observed association was not solely due to group differences.
“The key take away is that we found an association between GLP-1 use and breast cancer incidence,” presenting author Elizabeth McDonald, MD, PhD, a professor of Radiology in the University of Pennsylvania Perelman School of Medicine and a practicing breast radiologist at Penn’s Abramson Cancer Center, told Medical News Today.
“If validated in a clinical trial, the observed reduction in breast cancer risk associated with GLP-1 use would be somewhat less than, but broadly comparable to, that seen with established preventive interventions such as bariatric surgery and anti-estrogen therapies,” she said.
“This is very exciting because breast cancer is one of the obesity associated cancers and bariatric surgery, while effective to reduce breast cancer risk, is not scalable at a population level.”
— Elizabeth McDonald, MD, PhD
“Additionally, estrogen blockers, while effective and necessary when recommended by a physician, have unfortunate side effects that reduce compliance and also limit their use to women at high risk of breast cancer,” she added.
However, as the study was observational, it cannot establish causation. Additionally, the study did not account for the type of GLP-1 medication or length of use, genetic risk factors, or cancer stage or type at diagnosis.
The researchers note that further analyses are planned to address some of these variables.
Excess body weight, particularly after menopause, is a well-established risk factor for breast cancer. As GLP-1 medications can produce significant and sustained weight loss, improvements in body weight and metabolic health likely play a role in the observed risk reduction.
However, the researchers suggest that additional mechanisms may also be involved.
Chronic low-grade inflammation can contribute to multiple cancers, including breast cancer. Research highlights that GLP-1 medications may possess anti-inflammatory properties, which may help create an environment that is less favorable for tumor development.
This reduction in inflammation can also help reduce insulin resistance, which is a primary driver of type 2 diabetes and can also increase the risk as well as affect the survival outcome of breast cancer.
Obesity and insulin resistance can also affect other pathways, such as the insulin-like growth factor system. Growing evidence supports an important role for this signaling pathway in breast cancer.
As such, GLP-1 medications could potentially affect many different targets and pathways associated with breast cancer development.
“We know that there are over a dozen cancers that are associated with obesity and breast cancer is one of them.
The increased risk for cancer associated with obesity is mediated partly by changes in the immune system. Hypertrophic adipocytes undergo phenotypic changes and begin to secrete inflammatory adipokines (bioactive molecules released from an adipocyte) and cytokines (immune signaling molecules involved in inflammation, immunity, and cell communication).
These act locally and systemically to induce persistent, low-grade inflammation that fails to resolve.
Obesity-associated adipose tissue thus functions as an inflammatory endocrine organ, particularly in visceral tissue producing TNF-α, IL-6, IL-1β, Monocyte chemoattractant Protein 1 (MCP-1, which is associated with tamoxifen resistance), and leptin while reducing adiponectin (an anti-inflammatory adipokine) levels, thereby promoting chronic low-grade inflammation, insulin resistance, and tumor-promoting signaling pathways.
This increases cancer risk by two distinct mechanisms – both through the promotion of chronic inflammation, and through inhibition of the acute inflammation that is important to halt tumorigenesis (anti-tumor immunity). GLP-1 analogs both increase adiponectin expression and reduce adipose-associated inflammation, including reductions in TNF-α, IL-6, and leptin.
Additionally, in the case of breast cancer, fat cells produce estrogen and the majority of breast cancers express estrogen receptors and grow in response to estrogen. So maintaining a healthy weight in peri-menopause and menopause is important.
GLP-1 agonists, through weight loss dependent mechanisms, reduce estrogen and inflammation. They also have metabolic effects and help decrease insulin resistance.
While it is plausible biologically and supported by clinical trials that weight loss alone would decrease breast cancer risk, GLP-1 agonists are likely working through other pathways.
We do not yet know whether they directly affect tumor growth and development independent of weight loss benefits, or if and how they impact the metabolic activity of tumors or influence inflammation within the tumor microenvironment.”
— Elizabeth McDonald, MD, PhD
Current options for reducing breast cancer in those at
However, while these options can substantially reduce breast cancer incidence in high-risk individuals, they can also result in adverse events.
If future clinical trials confirm a protective effect, GLP-1 medications could represent a new approach to breast cancer prevention, particularly among those already using the drugs for obesity or diabetes.
“If causality is established through a clinical trial, then the next step is to determine exactly what the mechanism of action is that leads to cancer prevention,” McDonald told MNT.
“There are so many implications – if there are cancer prevention pathways separate from those causing weight loss, then perhaps drugs could be developed that all, including normal weight women, could take to reduce breast cancer risk,” she said.
McDonald said that if a causal link is proven, thsi could have implicatiosn for otehr cancer types, such as lung, colon, and liver cancer, leukemia and multiple myeloma
“But observational studies all have some level of bias, despite sophisticated methods to control for this. The time is now for our country to invest in a prospective clinical trial to test this hypothesis and breast is the perfect tumor type to be the subject of such a trial since it is common and allows a cost-effective efficient design,” she added.
The research team is now working to launch a prospective, multi-site clinical trial that will examine whether GLP-1 medications can reduce breast cancer incidence in females at elevated risk, including breast cancer survivors.
“We are planning a multi-site international clinical trial called INSPIRE, a collaboration between the American College of Radiology Center for Research and Innovation and the Eastern Cooperative Oncology Group (ECOG-ACRIN),” McDonald revealed to MNT, saying they wre now trying to secure funding.
“We designed the study within the ECOG-ACRIN TMIST population, which includes more than 108,000 women worldwide who have been recruited, characterized for breast cancer risk, and undergoing regular screening for breast cancer,” she said.
For now, the study adds to a growing body of evidence suggesting that GLP-1 medications may influence health outcomes far beyond weight management. However, until randomized trials are completed, the results should be viewed as promising but preliminary.
