GLP-1 medications associated with lower breast cancer risk in large US study
A retrospective study suggests GLP-1 use is linked to lower breast cancer risk. The study analyzed data from 111,646 women aged 45-80. GLP-1 users had significantly lower odds of developing breast cancer. Findings were presented at the 2026 ASCO Annual Meeting. Further clinical trials are needed for validation.
Women using GLP-1 receptor agonists had approximately 30 percent lower odds of developing breast cancer compared with non-users, according to a retrospective analysis of electronic health records from 111,646 females aged 45 to 80 years within the Penn Medicine health system.
The findings, presented at the 2026 ASCO Annual Meeting and published in JCO Oncology Practice, showed a 35.1 percent reduction in breast cancer incidence in the full cohort and a 30.5 percent reduction in a matched cohort adjusted for age, race, ethnicity, body mass index, breast density and diabetes status. The data were collected between January 2022 and June 2025.
Elizabeth McDonald, a breast radiologist at the Abramson Cancer Center at the University of Pennsylvania and the study's presenting author, said the association remained significant after matching for known risk factors. "The key takeaway is that we found an association between GLP-1 use and breast cancer incidence," McDonald told the meeting.
The study was observational and cannot establish causation. McDonald said the observed reduction, if validated in a clinical trial, would be somewhat less than but broadly comparable to that seen with established preventive interventions such as bariatric surgery and anti-estrogen therapies.
Researchers analyzed electronic health records from women within the Penn Medicine system. The cohort included patients with body mass index of 25 or higher. The study did not account for genetic risk factors, cancer stage or tumor subtype.
Overweight and obesity are established risk factors for breast cancer, in part because excess body fat increases estrogen production. Estrogen stimulates the growth of hormone receptor-positive breast cancers, which account for the majority of cases. Obesity is also linked to chronic inflammation, insulin resistance and elevated insulin-like growth factors, all of which may promote tumor development.
Maintaining a healthy weight has been shown to reduce breast cancer risk. Obesity may also increase the likelihood of recurrence and poorer survival outcomes in patients diagnosed with the disease.
GLP-1 receptor agonists, a class of medications originally developed to regulate blood sugar and appetite in patients with type 2 diabetes, promote substantial weight loss. Growing evidence suggests the drugs may reduce overall cancer risk through multiple biological mechanisms, including weight reduction and potential anti-inflammatory effects.
McDonald said the findings prompted a clinical trial to determine whether GLP-1 medications have a true protective effect against breast cancer. "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," she said.
The researchers said further analyses are planned to explore additional biological mechanisms that might contribute to the observed association. The study did not examine whether the protective effect varied by cancer subtype or stage at diagnosis.
The Penn Medicine team said the results support further clinical research into the use of GLP-1 receptor agonists for cancer prevention. The medications, which include semaglutide and tirzepatide, have gained widespread use for weight management in recent years.
Bariatric surgery has been shown to reduce breast cancer risk by approximately 40 to 50 percent in observational studies, according to published data. Anti-estrogen therapies, such as tamoxifen and raloxifene, reduce the risk of hormone receptor-positive breast cancer by approximately 30 to 50 percent in high-risk women, per clinical trial results.
The study's matched cohort design aimed to control for confounding variables that might explain the observed association. Researchers matched GLP-1 users with non-users based on demographic and clinical characteristics known to influence breast cancer risk.
Chronic inflammation associated with obesity creates a microenvironment that may favor tumor initiation and progression. Insulin resistance and elevated insulin-like growth factors, both common in obesity, have been linked to increased cancer risk in multiple studies.
GLP-1 receptor agonists work by mimicking the action of glucagon-like peptide-1, a hormone that regulates blood sugar and appetite. The medications slow gastric emptying, increase insulin secretion and reduce glucagon release, leading to improved glycemic control and reduced caloric intake.
Weight loss achieved through GLP-1 medications typically ranges from 10 to 20 percent of body weight, depending on the specific drug and dose. This degree of weight reduction is associated with improvements in metabolic health markers, including insulin sensitivity and inflammatory markers.
The researchers said the study's large sample size and use of electronic health records from a single health system allowed for detailed analysis of patient characteristics and outcomes. The Penn Medicine system includes multiple hospitals and outpatient facilities in the Philadelphia region.
The study did not assess the duration of GLP-1 use required to observe a protective effect, nor did it examine whether the association differed by specific medication within the GLP-1 class. Further research is needed to address these questions.
McDonald said the findings add to a growing body of evidence suggesting GLP-1 receptor agonists may have benefits beyond glycemic control and weight loss. Recent studies have reported associations between GLP-1 use and reduced risk of cardiovascular events, kidney disease progression and other obesity-related conditions.
The 2026 ASCO Annual Meeting, held in Chicago, featured presentations on cancer prevention, treatment and survivorship. The meeting is the largest annual gathering of oncology professionals worldwide.
JCO Oncology Practice, the journal that published the study, focuses on research relevant to clinical oncology practice. The journal is published by the American Society of Clinical Oncology.
The researchers said a randomized controlled trial would be necessary to confirm whether GLP-1 medications directly reduce breast cancer risk or whether the observed association is due to confounding factors not fully captured in the matching process. Such a trial would require long-term follow-up to detect differences in cancer incidence.
The study's findings have implications for cancer prevention strategies in populations with high rates of obesity. In the United States, approximately 42 percent of adults have obesity, defined as a body mass index of 30 or higher, according to data from the Centers for Disease Control and Prevention.
Breast cancer is the most commonly diagnosed cancer among women in the United States, with an estimated 310,720 new cases expected in 2026, per American Cancer Society projections. Obesity-related cancers, including breast, endometrial, colorectal and kidney cancers, account for approximately 40 percent of all cancers diagnosed annually.
The researchers said the study's limitations include its observational design, lack of data on genetic risk factors and inability to determine the specific biological mechanisms underlying the observed association. The study also did not assess whether the protective effect varied by menopausal status, a known modifier of breast cancer risk.
McDonald said the team plans to conduct additional analyses examining the association between GLP-1 use and other obesity-related cancers. The Penn Medicine health system's electronic health records include data on multiple cancer types, allowing for similar retrospective analyses.
The study received no external funding and the authors reported no conflicts of interest related to the research. Several authors disclosed consulting relationships with pharmaceutical companies unrelated to the study.
GLP-1 receptor agonists are approved by the US Food and Drug Administration for the treatment of type 2 diabetes and, in some cases, chronic weight management. The medications are typically administered by subcutaneous injection once weekly or once daily, depending on the formulation.
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