Weight management,
GLP-1s, and shared decision-making

While the live webinar is over, join us through this self-directed continuing education activity for a practical discussion that brings together evolving clinical evidence and the real concerns patients bring to these conversations. We’ll explore the relationship between cancer treatment, weight gain, emotional health, and health-related outcomes; what is known — and still unknown — about GLP-1 use after breast cancer; the role of exercise and other weight-management strategies; and patient-centered communication that supports informed, shared decisions.

Learning objectives

After this webinar, you’ll be able to:

• Describe the relationship between weight gain, cancer treatment, and health-related outcomes.
• Explain the potential benefits, risks, and unknowns for GLP-1 use in patients with a history of breast cancer.
• Compare the benefits of exercise and other weight-management strategies.
• Explain patients’ practical and emotional concerns about weight gain and the varied approaches to its management.
• Apply strategies for shared decision-making with patients.

Continuing education available

Earn up to:

• 1.0 AMA PRA Category 1 Credit™ (Physicians)
• 1.0 ANCC contact hour (Nurses)
• 1.0 ASWB ACE continuing education credit (Social Workers)

The Live Learner Notification includes important information about the program, including how to submit your evaluation after the live webinar and claim your certificate. If you attended the live program on September 17, please be sure to click on the “Live” event link when you begin the evaluation process (based on the instructions in the Live Learner Notification starting at the end of p. 2). You must complete your evaluation and obtain your certificate by December 18, 2026.

Video & audio recordings

Watch or listen to the recording below, or read the transcript here.

This project is supported by Grant/Cooperative Agreement Number NU58DP007913 from the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention.

Transcript

Michelle Bronzo, MA, LPC, LCPC, LMHC, CT, FT (00:00:09):

Hello, everyone, and welcome to today’s healthcare provider program, Weight management, GLP-1s, and shared decision-making. We’re glad you can join us.

(00:00:17):

My name is Michelle Bronzo. I’m pleased to serve as your moderator and one of your speakers today. I’m a licensed professional counselor specializing in grief, loss, and oncology, and I serve on the Living Beyond Breast Cancer and Medical Advisory Board. In case you’re just getting to know Living Beyond Breast Cancer, or LBBC, they’re a national nonprofit organization that offers trusted information and a community of support to people affected by breast cancer.

(00:00:42):

This program falls under LBBC’s grant or cooperative agreement with the Centers for Disease Control and Prevention. Since 2011, LBBC’s initiatives under this agreement have focused on addressing the needs of two very important groups: young people with breast cancer and people living with metastatic breast cancer.

(00:01:00):

We chose this topic because we’ve heard from providers that patients are looking for guidance on weight management and GLP-1s, and that providers are looking for support in having these conversations.

(00:01:10):

Our speakers today, myself and Dr. Neil Iyengar, will help us explore the relationship between cancer treatment, weight changes, emotional health, and health-related outcomes; what is known and still unknown about GLP-1 use after breast cancer; the role of exercise and other weight management strategies; and patient-centered communication that supports informed shared decisions. You can see our learning objectives now on the screen. I’m excited to be here with you today and want to thank Dr. Iyengar for sharing his time and insights as well with us.

(00:01:41):

Before we begin, I’d like to share some information about today’s program. Please use the chat to connect and the Q&A feature to submit questions at any time. We ask that you frame your questions so they can be helpful to all participants. Our speakers will respond to as many questions as possible after the presentation. Today’s session is being recorded and will be posted on the program event page.

(00:02:01):

Continuing education is available for physicians, nurses, and social workers who attend the entire live session today. You can see more details on the slide. Also related to continuing education is the live learner notification. This document provides important details about the program, including accreditation disclosures, a link to the evaluation form, and how to claim your certificate after the webinar. The evaluation and certificate instructions can be found at the end of the document. We’ll add the link to the live learner notification to the chat. It was in your webinar reminder email, and you’ll also receive a message after the webinar with a link to this document.

(00:02:38):

Please be sure to submit your evaluation and claim your certificate as soon as possible and no later than December 18.

(00:02:43):

It’s now my pleasure to introduce Dr. Neil Iyengar. Dr. Iyengar is a board-certified medical oncologist specializing in breast cancer. He practices at the Clifton campus of Winship Cancer Institute of Emory University. Dr. Iyengar is co-director of the Breast Medical Oncology Program and director of Cancer Survivorship Services at Winship. He also is an associate professor of hematology and medical oncology at Emory University School of Medicine.

(00:03:12):

Dr. Iyengar’s research focuses on improving metabolic health to reduce breast cancer risk and mortality. At Memorial Sloan Kettering, he developed and led the Healthy Living Program, an evidence-based survivorship model that creates personalized lifestyle plans for people during and after cancer treatment. His work has received recognition from several organizations and his research has been supported by grants from the National Cancer Institute, American Cancer Society, Breast Cancer Research Foundation, Conquer Cancer, and others. We’ve included a link to Dr. Iyengar’s full bio in the chat if you’d like to learn more.

(00:03:47):

Dr. Iyengar, please join us on screen to share your presentation. I will now turn things over to you.

Neil M. Iyengar, MD (00:03:53):

Thank you so much, Michelle, for that kind introduction. And I just want to thank everyone for being here today and especially LBBC for the opportunity to present on this important topic. I know this has certainly gained a lot of attention given now new medical weight-loss therapies, but I’ll just start off by saying that we have known for quite some time that our metabolic health really does directly impact both cancer risk and cancer outcomes. But I think it has always been a challenge to implement interventions that optimize our metabolic health, particularly when somebody’s dealing with a new diagnosis of cancer or ongoing cancer treatment.

(00:04:45):

We are now in a new era where we have medical therapies that are very effective for optimizing metabolic status, but we also have to keep in mind that lifestyle interventions remain such a central component of optimizing metabolic health. So I hope that comes through in my presentation today.

(00:05:04):

What I’d like to do, I’m going to go ahead and share my slides here. I’d like to share with you some of the studies that we’ve been working on and highlight for you where we have knowledge and where we need more data because this is certainly an evolving field. And I’ll do this from both a safety perspective as well as an opportunities perspective, and hopefully this will become more clear as I go through some of the data.

(00:05:32):

I’ll just start with some of my disclosures here. None of these relationships will impact the subject matter which I’ll be speaking about today.

(00:05:41):

I’ll first start off with what my comments were alluding to, and that is that we’ve known for a very long time that metabolic dysfunction is associated with a higher risk of developing several cancers and a higher risk of cancer growth after a cancer diagnosis. And obesity, which is defined as a body mass index of 30 or greater, and that’s essentially your height in kilograms divided by, or I should say your weight in kilograms, divided by your height in meters squared. This has been known for a long time. Obesity is a classical state of metabolic dysfunction, but I want to be clear that it’s not just obesity. We have evidence that diabetes, pre-diabetes, insulin resistance, and cardiac health can also contribute to cancer risk and cancer outcomes.

(00:06:36):

Ultimately what we really need is a way to identify somebody’s metabolic health status. And it’s not going to be so simple as optimal or suboptimal, it’s a continuum. And so our team and many other teams are working on ways to continuously assess a person’s metabolic health as a way to inform what their cancer risk is, but also to help us determine what interventions from a metabolic perspective would be helpful for an individual either during or after their cancer therapy.

(00:07:14):

But where we started was with obesity as a classical example of metabolic dysfunction. And what you can see here is data from the American Cancer Society. I know this is a busy chart here, but I just want to highlight here that there are at least 13 different obesity-related cancers. Some of the more recent studies suggest that the number is closer to 25 or more types of cancer that are related to obesity and metabolic dysfunction. What I want to highlight in this slide here is if you look at these graphs, what they’re showing you is the incidence of each of these cancers based on age group. So if you look at the legend at the very bottom, which is really tiny here, you’ll note that each color and shape denotes a different age group with the blue squares representing the youngest age group of age 25 to 29 and the open orange squares representing the oldest age group in this study, ages 80 to 84.

(00:08:16):

What you’ll see in the graphs here is that those older cohorts are at the top of the waterfall, if you will, meaning that the highest incidence or the highest number of cases of those cancers are in the older cohorts, and that’s to be expected. We know that aging is associated with a higher risk of developing cancer. But if you look at the slope of the curves, you can get a sense of what the trends are. So in those older cohorts towards the top of those waterfalls, you can see that the slope, many of those curves are either slightly flat over the years or they’re even going down a little bit over the years. But if you look at the younger cohorts, take a look at the closed blue squares towards the bottom of the waterfalls, you can see that those curves are actually trending up a little bit.

(00:09:11):

This is concerning, especially for the youngest age groups here. And the American Cancer Society identified obesity and metabolic dysfunction as a major risk factor that’s on the rise in younger age cohorts. And we know that breast cancer, for example, is unfortunately going up in incidence in the younger cohorts. Now, I don’t think obesity explains all of it, but it’s certainly a major part of it. And it might also be more subtle metabolic dysfunction that’s contributing to that rise in breast cancer incidence. But fortunately, we’re now sitting on an era where we have very successful metabolic interventions. So I do think we will have major public health impact in terms of reducing metabolic associated cancers in the coming years, and we’re already starting to see some of those effects.

(00:10:03):

After a breast cancer diagnosis, we also have several studies which indicate that obesity and body mass index are associated with a higher risk of breast cancer recurrence. I’ve talked about the initial risk of breast cancer. That’s what the curve on the left here is showing, which is as a person’s body mass index goes up, so does their risk of developing estrogen receptor-positive, postmenopausal breast cancer. The association with premenopausal breast cancer is more complex and that’s a different topic.

(00:10:38):

When we look at the curve on the right there, what you can see here is that in patients who have been diagnosed with breast cancer, unfortunately having a high BMI of 30 or greater is associated with a higher risk of mortality or dying from the breast cancer. And we see that risk the highest for a BMI of 30 or greater. The risk is a little bit elevated for a BMI in the overweight range of 25 to 29, but you can see there that the risk is lowest for patients who have a normal body mass index of less than 25. That’s the gray line.

(00:11:17):

We’re learning we can be far more specific about characterizing an individual’s metabolic health beyond BMI by measuring body composition and insulin resistance levels and so forth. So more to come on this, but I just wanted to start off with this observation because this obesity-related observation is really what kickstarted the field in terms of trying to improve metabolic health to improve breast cancer outcomes.

(00:11:42):

I want to describe for you two of my own patients who were graceful and allowed us to share their cases. Of course, we’ll keep their identities anonymous. But I want to share with you these two cases because I think these are two situations that we commonly encounter in the clinic and that we’re thinking really hard about.

(00:12:06):

The first is a 56-year-old postmenopausal lady who was diagnosed with an early-stage breast cancer. This was a larger tumor, a T3 tumor, and it involved one of her lymph nodes. So her nodal status or nodal stage was N1. And it was a triple-negative breast cancer of the right breast.

(00:12:26):

We had recommended or planned to start chemo immunotherapy. This is known as the KEYNOTE-522 regimen, so it’s a combination of chemotherapy and immune therapy with Keytruda [pembrolizumab]. And she did have some other medical problems. She had obesity, she had a body mass index of 34, also diabetes, and she was on Metformin 1,000 milligrams bid. Her diabetes was fairly well controlled with a hemoglobin A1C of 6.2%.

(00:12:56):

Before she was diagnosed with breast cancer, she was really excited because she was getting ready to start tirzepatide, which is a GLP-1 and GIP dual receptor agonist that has been very successful in inducing weight loss. So her question was, Can she still start tirzepatide as she’s embarking on her immunochemotherapy for breast cancer? So we’ll come back to her case.

(00:13:20):

Another patient, this is a 42-year-old premenopausal lady who had an early-stage breast cancer, a smaller tumor, no lymph node involvement, and this was hormone receptor-positive, HER2-negative, involving her left breast. She had undergone a lumpectomy and radiation. She had a genomic risk score of 18, which puts her into the intermediate-risk range. And so no chemotherapy, but she was treated with ovarian suppression, Lupron, plus an aromatase inhibitor. Her BMI was below the obesity range but still in the overweight range at 29, and she had been on semaglutide, which is one of our earlier GLP-1 receptor agonists. She previously had an obese range BMI of 33, but on the semaglutide she had lost a significant amount of weight, bringing her BMI down to 29. But she had planned to continue semaglutide so that she could continue to lose weight. Well, we’re planning to start her adjuvant hormone therapy, and so her question is, Can she continue her semaglutide?

(00:14:26):

So we’ve got two cases here, one with triple negative, getting ready to start immunochemotherapy, and wanting to start a GLP-1 receptor agonist, and then a younger lady with hormone receptor-positive breast cancer who’s getting ready to start hormone therapy who’s been on a GLP-1 receptor agonist, wondering if she can continue that.

(00:14:48):

So we’re going to come back to these two cases towards the end of the talk here because now I want to show you some data which helps to inform how we might approach people that are in these situations.

(00:15:02):

I think one of the first things we recognize is that weight gain is a major issue after breast cancer diagnosis. In fact, the majority of patients unfortunately do gain weight after a breast cancer diagnosis, and this is due to a number of reasons. But we also know that weight gain can increase the risk of a breast cancer recurrence.

(00:15:24):

So if you look at the red box at the bottom, we can see that weight gain is associated with a higher risk of dying from any cause, and that’s generally because we know metabolic dysfunction increases the risk of cardiometabolic diseases — heart attacks, high blood pressure, hypertension, those sorts of things. But it also has an impact on the breast cancer, and that’s the yellow box on the top there. You can see that the risk of breast cancer recurrence or dying from breast cancer does go up with weight gain.

(00:15:54):

Now, these data are observational, and it’s based on an analysis of 12 studies that were pooled together. And certainly the treatment of breast cancer has progressed after this study was published, but it does give us some important thresholds to keep in mind.

(00:16:10):

First of all, you can see that people who gained more than 10% of their baseline body weight, that’s really where the risk is. The 5% to 10% weight gain, it does pose maybe some minor increase in risk. In some studies, it did not increase the risk. So I generally use that as a benchmark when I’m speaking with my patients is that we really want to avoid gaining more than 10% of what your body weight was when you were diagnosed with breast cancer. Of course, that can be a challenge because chemotherapy, hormone therapy, all of these are associated with weight gain. But that 10% threshold at least gives us a goal to avoid.

(00:16:54):

We also know from several studies that weight loss in people who are dealing with a BMI of 27 or above can improve many biomarkers and can actually improve the breast tissue, the status of the breast tissue, itself to lower the risk of breast cancer or a breast cancer recurrence. Our group and many other groups have done many studies looking at the biology of the breast tissue.

(00:17:20):

For the sake of time, I won’t go through it in detail, but I will say the panel on the left there is showing that in the setting of obesity, we see that the fat tissue in the breast, and the breast is made up 80% of fat tissue, that that fat tissue becomes inflamed. You can see this under a microscope. These are called crown-like structures of the breast. That’s the CLSB acronym there. That’s basically a fat cell, which is that yellow cell. It becomes surrounded by macrophages, which are immune cells, and that’s a very highly inflammatory focus. That spits out inflammatory cytokines. That’s that kind of alphabet soup you’re seeing there, IL-6, TNF, alpha, PGE2. These are all inflammatory cytokines. Their normal role is to help to heal a wound, but when the fat tissue is constantly inflamed, those cytokines serve as growth factors for tumors and they can prompt tumor growth.

(00:18:21):

That inflammation can also promote or increase estrogen production, not from the ovaries, but estrogen production within the fat tissue of the breast itself, which can also support the growth, of course, of estrogen receptor-positive breast cancers.

(00:18:36):

In animal models and in human tissues, several groups have now shown that weight loss through diet and exercise can reverse a lot of those processes and reverse the inflammation, reduce the estrogen production in the breast tissue, and ultimately lower breast cancer cell growth.

(00:18:54):

But the question then is exactly how much weight loss is necessary to reverse those processes. And several groups, and here I’m showing a study that was reported by Dr. Fabian and Dr. Hursting’s group, which essentially showed in both humans and in animal models, you really need a significant amount of weight loss, more than 10% of your body weight to reverse several of those processes. And most diet and exercise interventions will induce somewhere around 4% to 6% weight loss. So hitting that 10% weight loss has been a real challenge.

(00:19:30):

When we look at some of the big observational studies that have been published, we also get a clue in terms of how much weight loss we should be striving for.

(00:19:41):

The Women’s Health Initiative was a study that enrolled women who had not been diagnosed with cancer across the United States, and this was an observational study. In this particular analysis, about 60,000 women were included and followed for a median time of about 12 years. And in this study, what was observed was that losing at least 5% of body weight was associated with a 12% reduction in the risk of developing any obesity-related cancer. So this is showing us that it would be helpful to lose at least 5% of body weight, but this analysis does not tell us how far should you go. Is 5% enough? Should you go to 10%? Should you go to 15%?

(00:20:30):

We have some other analyses to help guide that question. The study in the middle here is the Look AHEAD Randomized Control Trial, which was a prospective randomized control trial for patients with overweight and obesity and Type 2 diabetes. And in this trial, participants were randomized to either participate in a weight loss lifestyle diet and exercise intervention arm or a control arm.

(00:20:57):

The purpose of this trial was not breast cancer prevention, it was to improve weight loss and diabetes, but there was a secondary analysis that was done later to see if it also helped to prevent breast cancer. And essentially what was found here was that in the patients in the weight loss arm — and the average amount of weight loss there was about 7% weight loss — there was a 16% reduction in obesity-associated cancers. So this is another clue that perhaps more weight loss is associated with a greater reduction in the risk of developing obesity-related cancers.

(00:21:37):

Well, if we go to the other extreme, and that’s bariatric surgery, which is essentially lap band procedures or more invasive procedures where you decrease the size of the stomach, these are the most successful procedures at inducing weight loss, and they can induce weight loss of more than half a person’s body weight.

(00:21:56):

In this particular study, this was an observational study that included a little over 30,000 patients with 6 years of average follow-up time. In the patients that underwent bariatric surgery, there was a 32% reduction in obesity-associated cancers. And in the curves in the bottom there, you can see that the patients that lost the most amount of weight, which was quartile four, that was losing more than 39% of total body weight, this really minimized their cancer risk.

(00:22:27):

Ultimately, if a person is struggling with obesity, it does appear that getting that body mass index back into the normal weight range, even if a person needs to lose large amounts of weight, does quite significantly protect someone from the development of obesity-associated cancers.

(00:22:47):

Now, of course, bariatric surgery is not the right solution for everyone. So until we had some of the GLP-1 receptor agonists, it was a real struggle to figure out what are the successful weight loss strategies to minimize a person’s risk of developing obesity-related cancers.

(00:23:04):

After a cancer diagnosis, the same question remains, and that is how much weight loss should a person who’s struggling with obesity strive for to reduce their risk of a breast cancer recurrence. Well, you may have heard of the ongoing breast cancer weight loss trial or the BWEL trial, which is led by Dr. Jennifer Ligibel from Dana-Farber. This is a multi-institutional, multinational study that has actually completed accrual. It accrued over 3,000 women with stage II and stage III breast cancer. It could have been hormone receptor positive or triple negative, and patients had to have a body mass index of 27 or greater. And the participants were randomized to a health education intervention, which was a telephone-based 2-year counseling arm, or a control arm, which is essentially self-directed. Patients were provided with the educational tools and materials, but it was up to them to implement a lifestyle intervention.

(00:24:05):

The bottom line here is that at about 12 months, patients in the intervention arm had lost about 5% of their baseline body weight. We’ve actually seen more updated data, 2 years out, where about 5% body weight loss was maintained in the intervention arm. Now, we’re waiting for the data to mature in this study, so longer follow-up time to address the question of whether 5% weight loss in this trial is enough to lower the risk of breast cancer recurrence.

(00:24:39):

I will say I’m in high suspense about this because I think maybe for some patients 5% is enough, but for others it may not be enough. And so this data will be really helpful in trying to identify who those patients are that benefit from a 5% weight loss threshold and who might need to strive for more.

(00:25:01):

Our group has conducted a more intensive weight loss trial in a smaller population, a proof of principle trial, if you will, which was a phase II trial funded by the American Cancer Society where we prescribed the exercise and each session was supervised in the patient’s home by an exercise physiologist. We also prescribed the diet. So on a weekly basis, we calculated the protein, carbohydrate, and caloric needs of each patient. And we worked with a company called Plantable to then ship the food that was prepared for each individual to the homes of these patients so that we could provide a highly individualized diet and exercise intervention versus a control arm, which was modeled after the BWEL study, a telephone counseling arm.

(00:25:51):

All of the participants, again, were wonderful to volunteer their breast tissue so that we could study how this would change the breast tissue microenvironment. This is a lot of data on this slide here, but I’ll just give you the bottom line. In the highly intensive diet and exercise arm, this was a 6-month intervention, the average amount of weight loss was 16% of body weight. And again, this really goes to show that you can achieve significant amount of weight loss through diet and exercise. Now, it’s not easy, and we were really providing a highly structured intervention for these patients, but that’s the level of weight loss that we see with GLP-1 receptor agonists.

(00:26:36):

In the control arm, the telephone-based counseling arm, the average amount of weight loss was also 5%, similar to what we saw in the BWEL trial. But what really grabbed our attention is what you see in the waterfall plots here, and that’s body composition. In the intervention arm, that’s the blue bars here, you can see that most patients actually gained lean mass, that’s panel C on the bottom there, which is really exciting because one of the concerns we have with GLP-1 receptor agonists is that when you lose a ton of weight, you also lose some lean mass, some muscle mass. And particularly for patients dealing with a cancer diagnosis, muscle mass is incredibly important as a method to improve insulin resistance.

(00:27:21):

Here we show that a lifestyle intervention can be successful not only at inducing significant amounts of weight loss, but can actually improve or increase muscle mass simultaneously.

(00:27:34):

Of course, this takes a lot of effort, both on the patient side, but also on the provider side to provide all of this counseling and resources. So now the question is, can we leverage the GLP-1 receptor agonists to do some of this weight loss for us.

(00:27:50):

Just a quick reminder of what the GLP-1 receptor agonists are. They were originally developed to treat diabetes because what they do is they normalize glycemic control. GLP is essentially a hormone receptor. And so what this helps to do is to rebalance that hormonal imbalance that can happen in diabetes, which is really attractive because some diabetes drugs can actually push a person over the ledge and make them hypoglycemic and drop their blood sugars too low. But the GLP-1s do not do that because what they’re really doing is restoring your natural homeostasis to maintain glycemic control.

(00:28:34):

A couple of years into the development of the GLP-1 receptor agonists, it was also noticed that they were inducing significant amount of weight loss, and now several of these drugs are approved specifically for obesity treatment independent of the diabetes indication. What we’re learning through a lot of ongoing studies is that these drugs seem to have a favorable effect on multiple tissues throughout the body. And what I would submit to you is that what I think this really is reflecting is that metabolic health impacts almost every single tissue in our body, and I think that has been under-recognized. And now with the GLPs, we’re seeing improvements in many tissues in the body from brain to skeletal muscle. And again, I think this underscores that our metabolic health is really enmeshed in the health of all of our tissues.

(00:29:30):

We saw a ton of data that came out at ASCO this year with regard to the use of GLP-1 receptor agonists and cancer. So I wrote about this for a couple of the journals and that’s all been published, but then I went to Claude and I said, “OK, AI, do your thing and summarize all of the data.” And I have to tell you that the output was completely wrong. What I did was I basically kept all of the nice boxes that it created for me, and then I went in and I redid all of the data. So just be careful what you find on AI out there.

(00:30:08):

But ultimately what we saw at ASCO was that the use of a GLP-1 receptor agonist reduced the risk of several obesity-related cancers, particularly in people at high risk with the body mass index of 30 or greater. We also saw that it reduced progression to metastatic disease after an individual was diagnosed with breast cancer, and that was also observed with non-small cell lung cancer, colorectal cancer, and hepatocellular carcinoma. And these drugs also improved overall survival for patients dealing with obesity and a cancer diagnosis.

(00:30:48):

So very exciting, but I have to point out some limitations here, and that is that this is observational. The data is only as good as the databases, and there have been some questions about the accuracy of some of these databases. We really need prospective trials to figure out how to individualize these tools and use them in the most optimal way.

(00:31:11):

One of the things that I’ll highlight here are two studies that I thought were particularly interesting. This was a study in patients with Type 2 diabetes, and the use of a GLP-1 receptor agonist was associated with a 7% reduction in the development of obesity-related cancers.

(00:31:29):

Now, if you look at populations that include patients without diabetes, that effect seems to increase, which is interesting. This is a study where about half of patients in this study had diabetes, half of the patients did not have diabetes. They all had obesity. And using a GLP-1 receptor agonist lowered the risk of obesity-related cancers now by 17%. So an even greater effect, again, highlighting that these tools might be really useful for reducing cancer risk and improving cancer outcomes.

(00:32:02):

What about the biology of the GLP-1 receptor agonists? I just want to quickly highlight what I found to be a really interesting study by one of our collaborators who’s a laboratory scientist, and I’ll just put all the data up on the slide here.

(00:32:17):

Basically what they did was they used mouse models of obesity. So these were obese mice with several different types of breast cancer, and they were fed a low-fat diet or a high-fat diet and treated with tirzepatide. The bottom line here is that, of course, as we knew, obesity, high-fat diet, accelerated the growth of breast cancer tumors. When the mouse was treated with tirzepatide, it decreased the tumors. It had an antitumor effect, but in the mice that were treated with calorie restriction — chronic caloric restriction, that’s the CCR bar you see in the middle of the slide there, the blue bar — that had the best effect against the tumors. In other words, shrinking the tumors was most effective through calorie restriction rather than tirzepatide. Now, tirzepatide had a good effect also, but again, calorie restriction was the most successful way to shrink tumors.

(00:33:19):

In the chart on the right there, again, calorie restriction was the most successful at reducing glucose and insulin levels. Tirzepatide also reduced glucose and insulin levels, but not to the level of calorie restriction.

(00:33:32):

Now, we know that mice are not humans, and in humans we live complex lives, so calorie restriction can sometimes be a challenge. So this is not to say that we should only do calorie restriction. Tirzepatide or other GLPs are attractive options here. But we can’t forget the importance of calorie restriction or diet and exercise intervention.

(00:33:52):

I’m running low on time, but what I want to highlight here is the fact that we are cautious because there is one study that has come out of the University of Texas which has shown us that the GLP-1 receptor agonists might actually reverse the beneficial effects of immune therapies. And that I think is because, first of all, some immune cells have GLP-1 receptors, and the other piece is we’re not fully understanding all of the immune effects of GLP-1 receptor agonists. And until we understand those effects better, I think we have to be very careful about using a GLP-1 receptor agonist during immune therapy for cancer treatment.

(00:34:37):

There are ongoing trials that are testing this, but I want to highlight here that I do think for some people, the GLP-1 receptor agonists can be a wonderful intervention. But again, we cannot forget about lifestyle and diet and exercise. That’s what this study or this paper is highlighting here is that we need to follow a healthy diet and focus on certain micronutrients that are listed on this slide here and healthy fat consumption as well as protein and fruit and vegetable consumption, which are also listed on this slide here. If you do this in conjunction with off and on GLP-1 receptor agonist use, I think that this will likely be the most successful strategy at maintaining metabolic health and improving cancer risk and outcomes.

(00:35:27):

If we go back to our cases here, for our patient who was 56 years old and dealing with a triple-negative breast cancer diagnosis about to start immunochemotherapy, I would not recommend starting tirzepatide at this time until we have more data on the safety of combining with immunotherapy. Perhaps she could start tirzepatide later on down the road after she’s completed her immunotherapy for breast cancer treatment.

(00:35:54):

For our 42-year-old with hormone receptor-positive breast cancer who’s been on semaglutide and who is about to start hormone therapy for breast cancer, we do have some evidence that a GLP-1 receptor agonist might actually improve outcomes in that setting and actually might prevent the weight gain associated with hormone therapy. So for that situation, I would recommend continuing the GLP or even starting a new GLP-1 if the patient has not started one yet and they’re dealing with a BMI of 27 or greater.

(00:36:27):

So again, we need to take an individualized approach and there will be some upcoming guidelines — this is from the European Society of Medical Oncology — that will enshrine those recommendations to help our providers guide our patients better in terms of where to use a GLP and perhaps when not to use a GLP.

(00:36:49):

I know we’re running low on time and I want to save time for questions and answers. So I’ll just end by shamelessly plugging an upcoming survivorship meeting on February 6 in Atlanta. If you’re interested in hearing more about this and much more about lifestyle interventions, please join us. The website is at the bottom there.

(00:37:12):

We hope to see you there, and I hope this was helpful. And with that, I’ll conclude and pass it back to you, Michelle. Thank you.

Michelle Bronzo, MA, LPC, LCPC, LMHC, CT, FT (00:37:19):

Thank you so much, Dr. Iyengar. I feel so grateful to get to listen to this presentation along with all of the listeners on this call because it’s such an emerging field, and I’m really happy to learn more about the medical side of things for our patients. However, we know that medical decision-making is not purely medical, and we also have patients that are coming to us that are not just obese that are looking to be on these GLP-1s and that these GLP-1 medications have helped and will continue to help many, many people. But they aren’t for everybody. So today I’m going to talk about the mental health considerations that providers should be thinking about when GLP-1 medications enter the picture.

(00:38:00):

GLP-1s don’t just change weight, they change appetite, they change our eating patterns, the way that we use food as reward, our social experiences around food, and the way that a person relates to their body. And we know that breast cancer itself can profoundly affect a person’s relationship with their body, their body image, their identity, their feelings of control. So today I want to focus on the intersection of those two things and what we as providers can be listening for so that we can support our patients in informed decision-making without inadvertently reinforcing weight stigma or disordered eating.

(00:38:37):

Why does mental health matter? I think that there are three reasons that this conversation’s particularly important. Number one, weight and appetite are extremely emotionally loaded topics. It’s tied to shame and self-esteem, the way that we connect socially to others, trauma, our past experiences, our family experiences. And secondly, cancer can profoundly disrupt a person’s sense of control over their body. You of all people know that, changes in the person’s body they didn’t ask for due to chemotherapy and surgery and treatment-induced menopause and all the things. So that is also an extremely important component in the mental health picture. And that GLP-1s themselves alter hunger and reward and self-perception.

(00:39:26):

So we’re taking something that already has a lot of emotional meaning — food and weight and body image — and then we’re introducing a medication that can substantially change the experience of hunger and eating. We really need to look at the individual sitting in front of us rather than just assuming that weight loss is psychologically beneficial.

(00:39:51):

We certainly need to look at it from a cultural perspective. GLP-1s have been framed kind of like a miracle drug all over social media. Celebrity use has dramatically increased their visibility. We see these before-and-after transformations, these dramatic weight loss stories, and tons of messaging about how someone’s life got better once they were thin. It’s everywhere. It’s in TV and sports and the arts world. This reinforces what we already know to be true about diet culture and the thin ideal. We’ve recently seen a re-emergence of that extremely thin look from the 1990s. They used to call that the “heroin chic” look.

(00:40:32):

For patients living in larger bodies, this intensifies stigma and creates the message that their body is something that needs to be fixed.

(00:40:43):

GLP-1s also are causing tension with the health at every size framework and the body positivity and fat liberation movements because these are working to challenge discrimination against larger bodies and the increasing medicalization of weight loss because we know that weight stigma doesn’t disappear when someone enters the healthcare setting. And actually in one study, more than half of patients with obesity reported experiencing stigmatizing or judgmental comments from their doctors and that size-based bias contributed to misdiagnosis and to reduce quality of care.

(00:41:24):

As providers, we don’t necessarily need to take any sort of position on the cultural debate being had, but we do need to recognize that our patients are living within it and that it’s a part of their overall decision-making picture.

(00:41:42):

What actually changes when someone starts a GLP-1? You heard about the medical piece, but inside the body, there’s a reduction in hunger cues and what we call food noise. That’s that persistent preoccupation with food. It’s the internal chatter that you might hear, “What am I going to have for dinner? When am I going to have that cake, that cookie?” Some people have a lot of food noise, some people have a little bit of food noise, but it really can reduce high food noise for people that are experiencing that. It changes reward pathways where food can become less pleasurable. Cravings can decrease, especially for highly processed foods and for alcohol, which — hey! — those are good things to have a reduction in intake. But there also can be some negative consequences socially. If someone socializes in a way that’s interwoven with food, if they’re having meals out with friends or holiday meals and they’re having appetite loss from their GLP-1s, that can really interfere in those settings.

(00:42:49):

Psychologically, I think there also can be another unexpected consequence where for some people, food may have been serving a purpose beyond nutrition. For a lot of people, eating can be a coping mechanism. It’s how people manage their overwhelm and their anxiety and their loneliness and their grief. If we take away something that people have been relying upon as a coping mechanism during what’s already an extremely stressful time — when they’ve had a cancer diagnosis or they’re going through treatment or they’re entering into survivorship — we need to ask, What replaces it? Do they have enough support without it?

(00:43:33):

There’s some emerging research looking at mental health outcomes regarding GLP-1 use. One large 2024 study found that people with obesity taking GLP-1s had a slightly increased incidence of anxiety and suicidal behavior compared with controls and almost twice the risk of developing major depression. This doesn’t determine causation by any means, but it does show the importance of monitoring mental health rather than just assuming that these medications are psychologically neutral.

(00:44:09):

So why might our patients be motivated to take these drugs? They may be particularly interested due to a desire for control over their life and body. You all know that cancer takes away a tremendous amount of control from people and weight is something that feels controllable. So it’s pretty psychologically appealing to get that control back.

(00:44:33):

There’s also a connection between weight and fear of recurrence. Dr. Iyengar spoke about how excess body fat is associated with cancer recurrence. Therefore people think if I lose weight, I’m doing something to prevent my cancer from coming back. So that’s a huge motivator.

(00:44:49):

People are also motivated by body image issues. We know that the physical changes following breast cancer treatment can be profound. If you’ve had a mastectomy, you’ve lost your hair, you’ve had lymphedema, really distressing to someone whose identity is tied to their appearance.

(00:45:13):

Some oncology specific concerns, Dr. Iyengar was talking about the nutrition and muscle mass concerns. GLP-1s are designed to reduce how much somebody eats. So that means that they’re going to be getting less protein, fewer essential nutrients. For someone who’s otherwise healthy, that may be pretty manageable. But for cancer patients, they’re probably already dealing with nutritional challenges. They’re going to have taste changes — that metallic taste and GI symptoms.

(00:45:49):

Fatigue. If you’re so tired that you can’t shop or prepare meals, you’re not going to have a lot of energy to eat and therefore your nutrition’s going to be impacted. And we need to remember that poor nutrition makes the body weaker. So what happens if we add a medication that further suppresses appetite?

(00:46:08):

There’s also an overlap between treatment side effects from cancer treatment and GLP-1 side effects. So if you have nausea from chemotherapy and then you’re also experiencing nausea with the GLP-1s, that further impacts your nutrition.

(00:46:25):

And truthfully, I think at the heart of all this decision making, we see this a lot in our cancer care, is that tension between survival and quality of life. Someone shouldn’t have to choose between the two of those things, but I think people sometimes feel like they do. I can’t tell you how often I hear my clients say things like, “I’m so glad that I’m alive, but I feel so crappy in my body.” Or “I feel so upset about the way I look. I don’t want to look in the mirror. I feel like I’ve aged 10 years.” I’m sure you all have heard comments like that before. Similar to the talk that LBBC did last month on HRT and breast cancer, there’s this tension between those two goals.

(00:47:10):

What is our role?

(00:47:13):

I think our role as providers is certainly not to tell every patient whether or not they should take a GLP-1. Our role is to help patients make informed self-aware decisions while protecting their mental health and their relationship with food.

(00:47:28):

We want to start by assessing what does the patient already know about this. What do they understand about this medication? What do they expect it to do? What might they be worried about? How do they feel about GLP-1s in general?

(00:47:44):

Try to do this as objectively and neutrally as possible. We don’t want to be reinforcing any weight-based stigma or communicating that weight loss equals success in any way.

(00:47:58):

There are certain populations where we should be particularly attentive, and I really want you all to hear this. The first is anyone with a history of an eating disorder. Binge eating disorder, bulimia, anorexia, restrictive eating patterns. There actually is some limited preliminary evidence that GLP-1s may have certain benefits for binge-eating types due to that reduction in food noise and the compulsion to overeat. But on the other side of things for anorexia and the restrictive types, the research is very scarce and inconclusive, so we want to be really careful about that. And theoretically suppressing appetite, blunts hunger cues, it complicates intuitive eating. These are things that people with eating disorders already are pretty challenged by.

(00:48:49):

We also know that an eating disorder isn’t necessarily visible based on someone’s BMI. Restrictive eating can be very hard to detect, especially if someone doesn’t present classically with an underweight look. Someone can have a normal or even high BMI and still have severe restriction. They can still have extreme food rules. They can still have extreme what we call compensatory behaviors. Those are things like over-exercising or purging after a binge. And then we should also pay particular attention to adolescents, young adults, as well as people with anxiety, OCD, and perfectionistic traits. So certainly collaborate with any mental health providers that you may have on your team.

(00:49:40):

How do we start this conversation with our patients? One way to frame it could be something like, “Because medications like GLP-1s can affect appetite, weight, and how we relate to food, I’d like to learn a little bit about your personal history with eating and body image as well as your future goals.” And just because of time, I’m not going to read some of the questions that are here, but this is basically going through questions in general, asking about how they’re imagining their body might change due to GLP-1, what their health goals are. We’re asking about body image, and I know they’ll email the slides out afterwards so you can have these as well.

(00:50:21):

What we’re wanting to understand is, is weight loss one component of their overall health plan or is it the driving force? And then we want to screen for disordered eating. Have there been times when you felt out of control around food? Have you ever been diagnosed with an eating disorder? And then we want to assess whether or not the patient can maintain adequate nutrition through their treatment. This gives us a much more complete picture than simply looking at someone’s BMI or asking about their weight.

(00:50:52):

What are we listening for? Some red flags include meal skipping beyond what we’d expect from ordinary appetite reduction. I’ve listed some others here. I also want to say that reduced appetite isn’t automatically disordered eating. We want to look at the broader pattern of behavior that includes some of these red flags that are here.

(00:51:13):

Clinically, we’re trying to understand several things. Are there any signs of disordered eating? Is the person primarily motivated by health or by fear of weight gain? Are they able to maintain adequate nutrition? Breast cancer patients, especially those taking endocrine therapy, may experience less significant weight loss than GLP-1 use in the general population. So we want to assess expectations going in. What do they think is going to happen? How they respond if the GLP-1s don’t do what they’re hoping they will do, because unrealistic expectations can set a patient up for disappointment and escalation of distress, which we certainly don’t want.

(00:51:58):

Coming to an end here. I just want to let you all know that if concerns emerge for you while your patients are taking GLP-1s, there’s some interventions that can make a big difference. Psychoeducation around nutrition, certainly a referral to a registered dietitian who can help patients maintain their adequate nutrition and their protein needs, flexibility around their GLP-1 use. They may need to take a break. They may need to stop in order to mitigate side effects. And referral to mental health providers, therapists who

(00:52:35):

And I encourage you all to make a plan in advance with them. If challenges come up while you’re taking this medication, how would you want support?

(00:52:43):

Just to wrap up, GLP-1s have both physical and psychological effects. They’re not just a medication that makes someone lose weight. We know our cancer patients can be particularly vulnerable because treatment affects body image and identity profoundly, and that screening for whether someone’s at risk is essential. This doesn’t mean that someone shouldn’t take a GLP-1, but it means that we’re asking whether the medication makes sense for this particular person’s both physical and psychological health at this particular point in their cancer journey, and can we support them in using it safely.

(00:53:22):

Dr. Iyengar, this is for you. How much weight loss is helpful in early and advanced breast cancer versus risk of being compromised during treatment? Are there differences in GLP-1 use in people with early-stage breast cancer compared to metastatic?

Neil M. Iyengar, MD (00:53:36):

Yeah, that’s a great question.

(00:53:38):

I would say first of all, my preference is actually to focus on body composition over weight loss. If somebody has a body mass index above 27, I would say, yeah, the first goal would to try to be to get your body mass index to 27 or below, ideally 25, but it needs to be done slowly. So I also would emphasize the speed of weight loss is important because we’ve actually done studies showing that rapid weight loss is actually detrimental and causes more inflammation. You want to aim for around 1 to 2 pounds of weight loss a week. The sweet spot is about 1 pound a week. Once you start getting higher than that, then I would worry that it’s going too fast. And so that’s the first piece.

(00:54:38):

And then the second piece is aim for getting your BMI under 27, under 25 ideally. But perhaps the most important is body composition. And this is where I would actually recommend either at your PCP’s office or many gyms have body composition machines. In our clinical trials, we use a Withings scale. You can buy it on Amazon. It’s called the Withings Body Plus Scale. Now, it is more expensive than a regular scale. I think it’s about $100. But I do recommend following body composition, and there I would advocate for a total body fat level less than 30%. That’s where we start to see the risk decrease. That could be probably the best way because you also want to monitor your lean mass. And ideally, while you’re losing weight at a slow and steady rate, your lean mass is at least staying the same. Or if you’re adding in resistance exercise, perhaps you’re bumping up your lean mass as well.

(00:55:44):

I hope that wasn’t too complex, but those are the pearls that I would try to pursue with weight loss.

Michelle Bronzo, MA, LPC, LCPC, LMHC, CT, FT (00:55:50):

Fantastic. Thank you.

(00:55:51):

And can you talk about the risk and benefits of GLP-1s in terms of developing new cancers? It’s been noted that these medications may help with losing weight, but you can run the risk of developing a new cancer such as thyroid cancer or pancreatic cancer.

Neil M. Iyengar, MD (00:56:06):

Yeah, this is a great question. I would say that it’s still a bit controversial. The thyroid cancer risk was observed in a couple of the phase III studies and in some, but not all, of the observational studies.

(00:56:19):

What I would say is that the thyroid cancer risk could either be because it was independent and unmasked from the weight loss or it could be a direct effect of the GLP. So in that setting, what was reassuring was that the thyroid cancer that developed in most of those rare cases was a more indolent, highly treatable type of thyroid cancer, typically treated with resection or partial thyroid resection.

(00:56:50):

The risk-benefit ratio does seem to still favor the use of these agents. The pancreatic cancer risk, we’ve seen mixed data where in some studies there’s a slight increase in risk, in others there’s no increase in risk. And I do think that the status of the pancreas matters. Do the people in those studies have diabetes? Is it insulin-dependent diabetes or non-insulin-dependent diabetes?

(00:57:18):

I think the bottom line is we just don’t have a clear picture of whether or not the GLPs are truly driving those cancer risks. But to be very cautious, I would say that we certainly need to make sure that a person on a GLP is following closely with a medical provider for appropriate cancer screening.

Michelle Bronzo, MA, LPC, LCPC, LMHC, CT, FT (00:57:37):

What do you suggest for people with borderline BMI — 25, 26 — who are worried about gaining weight due to endocrine therapy-induced menopause? My oncologist and PC are hesitant to prescribe a GLP-1 at this time, but I’m worried about getting ahead of the issue possibly with microdosing.

Neil M. Iyengar, MD (00:57:56):

Yeah, it’s a great question. And so I skipped the part of my presentation where I actually had a few slides on some studies that we’ve done in a situation called normal-weight obesity where your body mass index is actually normal, that’s less than 25, but the body fat level is elevated. And we’ve seen similar increases in the risk of breast cancer and breast cancer recurrence as classical obesity in the setting of normal-weight obesity. That’s where the 30% body fat threshold comes from. We see that in the setting of normal BMI and a body fat level above 30%, the risk of breast cancer recurrence and incidence increases.

(00:58:36):

I would say for a person in that situation, this is actually the ideal situation for lifestyle intervention, a combination of aerobic plus resistance training. It’s not going to be the classical calorie restriction energy expenditure to burn calories. It should be more focused on body recomposition. And there are some great platforms out there that I would recommend to pursue. The American Cancer Society has survivorshine.org, which is a great lifestyle intervention portal that you can log into or recommend to your patients to use. The American Institute for Cancer Research, or AICR.org, also has great information on this.

(00:59:17):

The use of a GLP in that setting, I think that if for this particular question, if you’re doing all the lifestyle interventions and you’re watching your body composition but you’re on the hormone therapy and your weight is still creeping up despite all of this, I think that is an area where we’re planning to study the use of low-dose GLPs. But until we have data in that setting, I would stick to the indication for a GLP, which is either classical obesity or overweight plus a metabolic disorder.

Michelle Bronzo, MA, LPC, LCPC, LMHC, CT, FT (00:59:49):

Great.

(00:59:50):

At this point, this is all the time we have for questions. I know that you all probably have questions that you could ask for hours. It’s such an important and interesting topic, but on behalf of Living Beyond Breast, thank you Dr. Iyengar for sharing your expertise and valuable insights with us today. Thank you to our audience as well for being so engaged in today’s discussion. I’d like to again recognize the Centers for Disease Control and Prevention for their support of this program.