Glucagon-like peptide-1 (GLP-1) receptor agonists have transformed the management of obesity and type 2 diabetes, prompting growing interest in their potential applications across oncology. In breast cancer care, clinicians are routinely navigating patient inquiries regarding the safety, drug interactions, and oncologic effects of these agents. In this interview, Jasmin Hundal, MD, MS, MPH, discusses her co-authored review recently published in JCO Oncology Practice, exploring the metabolic, clinical, and survivorship implications of GLP-1 receptor agonists in breast cancer. She outlines the biological interplay between adiposity and tumor progression, the necessity of preserving lean muscle mass, and the critical need for prospective trials in this field.

Addressing Practical Clinical Questions

The widespread adoption of GLP-1 therapies in the general population has outpaced the generation of oncology-specific data, leaving clinicians to address complex practical questions without robust prospective guidance. As Dr. Hundal noted, “GLP-1 receptor agonists are increasingly being used in patients with obesity and diabetes, including many patients who have breast cancer, while the oncology-specific evidence still remains very limited.”

In daily practice, oncologists are asked to evaluate whether these agents interfere with systemic antineoplastic regimens and whether metabolic improvements translate into lower recurrence rates. “As an oncologist, we are asked practical questions about GLP-1 receptor agonists in the clinic almost every day—whether these medications are safe to use with endocrine therapy or with chemotherapy, what interactions they could have, what implications they have, and what we have to do to monitor?” Dr. Hundal explained.

At the same time, expanding biological knowledge highlights how adipose tissue actively drives oncogenesis. “Obesity does not simply refer to a number, as we have learned over the years,” Dr. Hundal said. She points out that “adipose tissue with metabolic-reactive and obesity-related dysfunction can influence estrogen production, insulin, IGF-1 signaling, inflammation, and some pathways that are relevant to breast cancer treatment, such as the PIK3CA pathway.”

Consequently, optimizing metabolic health should be recognized as an integral component of comprehensive oncology care rather than an isolated comorbidity.

Body Composition, Sarcopenia, and Functional Preservation

A critical consideration when prescribing GLP-1 therapies to patients with cancer is the nature of the weight reduction achieved. Because these medications can reduce lean body mass alongside fat mass, oncologists must guard against sarcopenia. “Some of the weight loss is lean body mass,” Dr. Hundal emphasized. “In cancer patients, we do know that sarcopenia, which refers to low muscle mass, is associated with treatment toxicities, functional decline, and dose reduction, and it can lead to complications and worse outcomes.”

To prevent functional decline, clinical management must emphasize lifestyle and nutritional countermeasures. “When we think about therapies in breast cancer, the goal should not simply be weight reduction, but we should look at muscle preservation, physical function, adequate protein intake, resistance training, and nutritional status, because all of these things play a very important role in preserving muscle mass,” Dr. Hundal observed. Maintaining this balance ensures that cardiometabolic improvements do not come at the expense of patient strength and treatment tolerance.

Distinguishing Enthusiasm From Prospective Evidence

Despite encouraging real-world observations and widespread media attention, definitive data proving that GLP-1 receptor agonists reduce breast cancer recurrence or prolong survival remain absent. Dr. Hundal cautioned against overinterpreting preliminary findings: “We need to be very careful on overstating the evidence that we have right now. We are seeing so many headlines in the newspapers or in abstract form, but we have to be aware that this is based on retrospective database studies, and we do need prospective studies.”

While GLP-1 therapies clearly offer meaningful glycemic and cardiovascular benefits, their direct oncologic impact requires formal investigation. “We just don't have the prospective data to certainly say that they reduce breast concerns or improve breast cancer survival,” she noted.

This work fits within the broader emergence of metabo-oncology, a discipline that recognizes host metabolism as an active participant across the cancer continuum. Dr. Hundal explained that “metabolic oncology is about recognizing that metabolism is not simply background patient information—it intersects with cancer biology, treatment, toxicity, and survivorship.” Moving forward, prospective trials must evaluate treatment timing, systemic drug interactions, and diverse endpoints—including body composition, patient-reported outcomes, and long-term adherence—to define how to integrate these agents safely into breast cancer care.

Conclusion

GLP-1 receptor agonists present promising opportunities to improve metabolic health, mitigate cardiovascular risk, and enhance survivorship for patients with breast cancer, but enthusiasm must be anchored in rigorous clinical evidence. Managing body composition, protecting against sarcopenic muscle loss, and monitoring concurrent cancer therapies remain essential responsibilities in current practice. By pursuing prospective studies that evaluate both metabolic indices and cancer-specific endpoints, the oncology community can determine how best to incorporate metabolic therapies into standard treatment paradigms.

Key Takeaways

Metabolic health directly intersects with breast cancer biology, treatment tolerance, and survivorship through estrogen production, insulin signaling, and inflammatory pathways.
The rapid clinical uptake of GLP-1 receptor agonists has created an urgent need for oncology-specific guidance regarding safety, drug interactions, and patient monitoring during systemic therapy.
Because GLP-1 therapies induce loss of lean body mass, clinical strategies must prioritize muscle preservation, adequate protein intake, and resistance training to prevent sarcopenia.
Current evidence suggesting that GLP-1 therapies reduce cancer recurrence or improve overall survival is retrospective, underscoring the necessity of prospective clinical trials.
Metabo-oncology represents a comprehensive care model that integrates pharmacotherapy, exercise, and nutritional interventions alongside standard antineoplastic treatments.

About Dr. Hundal

Jasmin Hundal, MD, MS, MPH, is a second-year Hematology/Oncology Fellow at the Cleveland Clinic in Cleveland, Ohio. Previously, she completed her Internal Medicine Residency at the University of Connecticut. Dr. Hundal’s main area of interest is the overlap between cardiometabolic health and cancer, particularly for breast cancer patients and survivors. Outside of work, she enjoys traveling, cooking, and hiking.

Metabolic Health Meets Oncology: GLP-1 Receptor Agonists in Breast Cancer