GLP-1 Agonists May Favorably Influence Metabolic Risk and Breast Cancer Outcomes

In this Q&A with Pharmacy Times, Joanne Mortimer, MD, FACP, FASCO, discusses emerging evidence on the safety and potential benefits of GLP-1 receptor agonists (RAs) in women with breast cancer. Mortimer explains that available data show no adverse short- or medium-term impact of GLP-1 therapies in patients with breast cancer and diabetes, while suggesting possible favorable effects through weight loss and reductions in adipose-driven inflammatory cytokines. She highlights the limitations of lifestyle-based weight loss interventions and notes that once-weekly GLP-1 agents may offer a more sustainable strategy for long-term weight control. Mortimer also addresses concerns about long-term safety, noting that current data suggest favorable effects on cardiovascular and cognitive outcomes.

Pharmacy Times: Can you go into a little bit about what potential biological mechanisms you think could be driving the survival benefit between GLP-1 RAs and breast cancer patients?

Joanne Mortimer, MD, FACP, FASCO: What I’d like to say is that we did not see any adverse impact of the GLP-1 agonist on women who had breast cancer and diabetes. In terms of possible mechanisms, we know that adipose tissue causes fat cells to create all sorts of cytokines that can aid in breast cancer cell growth. Presumably, if you decrease weight and decrease the volume of adipose tissue, you will, in turn, have an effect on breast cancer over the long term. That may be true for newly diagnosed patients if these drugs prevent the development of new breast cancers, as well as potentially having a favorable effect on people who have already been diagnosed with breast cancer.

Pharmacy Times: Given that prior weight loss interventions in breast cancer have had limited success, how do GLP-1s change the landscape in terms of realistic weight management strategies for this population?

Mortimer: Yeah, that’s a really wonderful question. Women with breast cancer who have been on interventions such as exercise programs, as long as they’re doing the exercise program and the diet, they will lose weight. The minute you withdraw that support and that coaching, patients go back to their pre-intervention weight, or beyond it.

I think the reason this seems to be more likely to keep patients controlled is because it’s once a week. They don’t have to exercise, and they don’t have to modify their diet. Their appetite dictates it, just based on the drug. Doing something once a week and not requiring exercise probably, unfortunately, makes this a strategy that is more likely to keep weight off patients.

Pharmacy Times: What reassurances can you offer regarding the safety of GLP-1s in breast cancer survivors, especially given ongoing public concerns about long-term effects or potential cancer interactions?

Mortimer: Yeah, you know, there certainly is always a concern that there will be long-term effects from these drugs, and certainly we have seen it. The longer-term side effects or benefits that we see with these drugs—memory and heart disease—suggest that the long-term effects are favorable, not adverse. So I think with the data that we have so far, what we can say is that there does not appear to be any adverse impact on breast cancer with short-term or medium-term follow-up.

Pharmacy Times: How do you envision the integration of metabolic therapies like GLP-1s into broader survivorship care models for breast cancer, especially for patients with obesity or metabolic syndrome?

Mortimer: I think these drugs are really going to be game-changing, and they have really altered public health in a favorable way. Patients who lose weight—we know there are certain things that have adverse effects on outcomes, especially in breast cancer, such as metabolic syndrome. We’ve done studies showing that chemotherapy causes metabolic syndrome in women who never had metabolic syndrome. Our drugs, in fact, cause metabolic syndrome, and patients who have metabolic syndrome do worse with breast cancer than patients who don’t have metabolic syndrome.

So presumably, by having these drugs incorporated both for managing obesity, which is an adverse factor, as well as metabolic syndrome, and hopefully incorporating these in the survivorship setting, that will have an impact long term. We need randomized studies to be done to look and see if GLP-1 agents really are safe and effective and help patients with breast cancer. We have studies that are in the process of being designed and conducted. So we don’t yet have the answer from controlled clinical trials, but the data that we have so far does suggest that the impact of these drugs is really favorable.