GLP-1 Agonists Poised to Impact Breast Cancer Care

Sherry Shen, MD

Breast Medical Oncologist

Memorial Sloan Kettering Cancer Center

New York, NY

Recent trends have brought GLP-1 receptor agonists, including semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound), to front of mind when discussing general weight loss. At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, multiple presentations focused on the weight loss aspect of GLP-1 agonists for patients with breast cancer. These data were mainly retrospective but ranged from specific patient groups, such as those with hormone receptor–positive disease receiving endocrine therapy¹ or those only receiving semaglutide and tirzepatide with stage I to III breast cancer,² to patients from the broader breast cancer population receiving a range of GLP-1 agonists.³

For the more general population, Sherry Shen, MD, and the other investigators of the study looked at patients with stage 0 to IV breast cancer with any receptor status. “[GLP-1 agonists] are being used as standard care, but we don’t know the effect on breast cancer outcomes, which is the most important thing,” Shen said in her interview with Peers & Perspectives in Oncology.

Peers & Perspectives in Oncology: Could you talk about whether weight gain is an adverse event (AE) in patients with breast cancer and how common it is?

Shen: Weight gain is a very common AE for many of our patients with breast cancer. Chemotherapy can induce weight gain. That’s contrary to what a lot of people and patients think. But we give a lot of fluids, we give steroids during chemotherapy, and patients completely alter their eating habits, whether that’s due to feeling nausea or queasiness or the period of chemotherapy with all the other new medications that are introduced. A lot of people may focus on carbohydrates rather than other types of foods during chemotherapy due to tolerability, which is OK but can contribute to weight gain. We know that during chemotherapy, other metabolic parameters worsen too. For example, insulin levels and hemoglobin A1C, which is a measure of glucose control, worsens [and] lipid profile components like total cholesterol, triglycerides, and low-density lipoprotein increase. Those can all get worse during chemotherapy as well.

Beyond chemotherapy, endocrine therapy pills, notoriously, can cause weight gain. It’s been variably reported in the literature. By that, I mean there’s a wide range of weight gain rate associated with these pills, but it seems that across the board, many of them cause or contribute to weight gain, some of which is related to menopause and the metabolic changes that come with that. Tamoxifen and the aromatase inhibitors can all contribute to weight gain. Our patients with hormone receptor–positive breast cancer make up 70% to 80% of patients with breast cancer, so most women are going on these pills at some point, even if they’re not getting chemotherapy necessarily. A lot of different breast cancer drugs can cause or contribute to weight gain.

Please discuss the goal of the retrospective study your ASCO poster is based on.

There is a lot of interest in GLP-1 agonists currently for many different reasons. But how can we use them in the cancer space, and are they relevant for breast cancer? What we set out to do was to look at patients with breast cancer at Memorial Sloan Kettering Cancer Center in New York.³ [We looked at] patients who had a diagnosis of breast cancer already and who received a GLP-1 agonist for whatever reason, [for] weight management or diabetes, at any point. Our main question was, are patients with breast cancer able to lose weight with these drugs? It was a small cohort of 75 patients with a history of breast cancer diagnosis at any point who had been prescribed a GLP-1 agonist within our system. I will say that historically, we made a lot of referrals outside of our system for weight management. So the vast majority of these prescriptions, almost 80%, were for diabetes and not for obesity or weight management.

What do you feel were the key takeaways? Did you find anything unexpected as you were conducting this trial?

What we found was that the average weight loss was about 5% with a GLP-1 agonist and that the longer patients were on the GLP-1 agonist, the more weight they tended to lose. At around 6 months from starting the GLP-1 agonist, it was over 2 kg. At 12 months from the GLP-1 agonist, it was over 4 kg. By the end of their GLP-1 treatment, it was over 6 kg of weight. We also looked at whether there were any factors, like the kind of breast cancer they had, whether it was hormone receptor positive, whether they were taking those endocrine therapy pills, and whether they had diabetes or didn’t have diabetes. We looked at all these to see whether that affected the amount of weight loss and whether certain characteristics were associated with a greater chance of having greater weight loss, and we did not find any significant associations. But that doesn’t mean that it’s not there. It’s just that this was a small cohort study, so we may not have seen a significant effect, and that may be different if we had a larger group of patients.

I don’t think there was anything surprising, but it was nice to see that patients with breast cancer who may or may not be taking these endocrine therapy pills can still lose weight with GLP-1 agonists. I would hesitate to compare the degree of weight loss that we saw in our study findings with the literature that’s out there in the phase 3 studies, because most of our patients, almost 80%, were getting the GLP-1 agonist for diabetes, not for weight management. So I don’t think it’s fair to that what we saw in our study was not as much as what we see in [findings from] the phase 3 trials. Five percent weight loss is still quite significant, and that’s very comparable to what people can achieve in lifestyle management trials. So it’s nice to see that there is weight loss, and this helps us get a sense of the effect size when we think about how we can use these drugs in clinical trials for breast cancer.

When you looked at the different factors, were you able to see what kind of GLP-1 agonist they were receiving?

We did [look at which GLP-1 agonist the patients received]. It was a small cohort, so we cannot and did not compare the different GLP-1 agonists. Forty-nine percent got liraglutide, 60% got semaglutide, 17% got exenatide, 8% got dulaglutide, and 11% got tirzepatide, which is Mounjaro and one of the newest agents. The percentages don’t add up to 100 because many of the patients, almost half, had used one and then switched to another, for example.

Were there any differences in treatment for patients who also had diabetes?

Because many of these patients got the GLP-1 agonist for diabetes, they got other concurrent diabetes medications as well. Most were on metformin. Some were concurrently receiving insulin or some of the other newer diabetes drugs like SGLT2 inhibitors, so that can certainly confound the degree of weight loss.

In patients with breast cancer receiving a GLP-1 agonist, do you feel there’s a potential for prescribing this consistently as AE management in the future?

That’s a great question. We as breast medical oncologists don’t prescribe these drugs. Our endocrinologists or our general internal medicine service helps us with that. I don’t personally prescribe and manage these medications, but there is a role in AE management, but not just that. We know that post–breast cancer diagnosis weight gain is associated with worse breast cancer outcomes. We’ve seen in [findings from] some of the major lifestyle trials that when there’s a significant degree of weight loss achieved, there can be a very modest but still significant improvement in breast cancer outcomes. There is a role to study these drugs for AE management, especially our patients on endocrine therapy. But in addition, with managing that AE, with decreasing the degree of weight gain that happens post diagnosis, perhaps there can be an effect on breast cancer outcomes.

That would be even more interesting and compelling as a reason to use this as part of standard care. But we have a lot of work that needs to be done before then, which is that this all needs to be studied rigorously in clinical trials.

How does the recent trend of using GLP-1 agonists as weight loss drugs for people without diabetes affect their use in clinical trials?

There are a lot of considerations there, one of which is availability of the drug. I think that’s going to be very hard if we have someone in a clinical trial who’s getting the GLP-1 agonist as standard care—in other words, billed to their insurance—but then they can’t get it for a month. That affects the outcomes of the clinical trial and affects accrual and how we manage those patients on study. So that’s a big consideration.

The other one is that so many patients are going to use this as standard care that we may not be able to find the right patients to initiate these drugs. All these [concerns] have to factor in when we design our clinical trials. But there may be patients who gain weight on study and then start to need these types of drugs too. There are a lot of different factors here and a lot of different settings in which it would be useful to study GLP-1 agonists in breast cancer.

REFERENCES:

1. Portillo DU, Mazo-Canola M, Alhaj S. Evaluating the impact of GLP-1 receptor agonists on weight management in patients with breast cancer undergoing endocrine therapy: a comparative analysis. J Clin Oncol. 2024;42(suppl 16):e13063. doi:10.1200/JCO.2024.42.16_suppl.e13063

2. Fischbach NA, Zhou B, Deng Y, Parsons K, Shelton A, Lustberg MB. Impact of semaglutide and tirzepatide administration on weight in women with stage I-III breast cancer. J Clin Oncol. 2024;42(suppl 16):e24140. doi:10.1200/JCO.2024.42.16_suppl.e24140

3. Shen S, Liu B, Fanti C, et al. Glucagon-like peptide-1 (GLP-1) agonist use and weight change among patients with breast cancer. J Clin Oncol. 2024;42(suppl 16):10607. doi:10.1200/JCO.2024.42.16_suppl.10607