Fármacos adelgazantes y cáncer de mama (seno)

Welcome to The Breastcancer.org Podcast, the podcast that brings you the latest information on breast cancer research treatments, side effects, and survivorship issues through expert interviews, as well as personal stories from people affected by breast cancer. Here's your host, Breastcancer.org Senior Editor, Jamie DePolo.

Jamie DePolo: Hello, as always, thanks for listening. 

According to a KFF poll, about one in eight, or 12%, of adults in the United States have used a GLP-1 agonist medicine. 

You likely know these drugs by their brand names, Ozempic, Trulicity, Victoza, Mounjaro, Wegovy, and Zepbound, to name just a few. These medicines were originally developed to treat diabetes, but quickly moved to being used for weight loss, reducing the risk of heart disease, and treating chronic kidney disease. 

Some research suggests that GLP-1 drugs may reduce the risk of cancer, but it's not clear if this is due to weight loss, or other mechanisms in the body. Other studies are looking at GLP-1 medicines to treat liver disease, depression, and polycystic ovary syndrome. 

While they seem like wonder drugs, GLP-1 medicines do cause side effects and have risks. GI problems, including nausea, vomiting, diarrhea, and constipation are common side effects. The drugs also can cause dizziness, headaches, and elevated heartbeat. The FDA requires a warning about the risk of medullary thyroid cancer on their labels. 

I'm joined by Dr. Neil Iyengar, a breast medical oncologist at Memorial Sloan Kettering Cancer Center. Dr Iyengar studies how diet and exercise can improve quality of life for people with breast cancer. He is going to help us understand how GLP-1 drugs work, and if there are any risks for people with breast cancer. 

Dr Iyengar, welcome to the podcast. 

Dr. Neil Iyengar: Hi. Thank you for having me. 

Jamie DePolo: So to start, very basically, so we all understand. Could you explain for us how these GLP-1 medicines work? What are they doing in the body? 

Dr. Neil Iyengar: Sure, absolutely. So the GLP-1 agonists are a class of drugs that fall under a broader class known as incretin mimetics. 

Jamie DePolo: That's a big term.

Dr. Neil Iyengar: Yes, yes. It's a bit of a tongue twister, but you know, it's just as the name sounds, a mimetic, which is essentially, the drug is mimicking what some of our hormones already do. And they, essentially, the GLP-1 receptor agonists, what they essentially do is they work by a couple of different mechanisms, and we're actually still learning about other mechanisms that we didn't even know they have. 

And I would categorize it as known and unknown mechanisms. And as far as the known mechanisms, what the GLP-1 agonists do, is they help to promote more insulin secretion. And by doing that, that helps to control our blood glucose levels, or blood sugar levels, and that, in fact, is originally why these drugs were approved to treat diabetes. 

Well, it also turns out that they help to slow gastric emptying. In other words, they help to slow down the speed of our digestion, and that, ultimately, helps us feel fuller. And this is the third mechanism, which is a sense of satiety, or feeling like you're now full.

And so, those are the main mechanisms, and again, from a diabetes perspective, it's helpful, because raising your insulin levels lowers your blood sugar levels, and the sensation of satiety, and slow gastric emptying helps people eat less, which can also decrease the blood sugar load. 

But it was quickly recognized that those effects were also contributing to weight loss, and ultimately, those same mechanisms do help with weight loss, but we are also learning — and now I'll jump into the unknown mechanisms — or the mechanisms that we're trying to learn more about.

And that's that it appears that the GLP-1 agonists have different functions in the different tissues in our bodies. And one of the interesting learnings is that these drugs appear to also change some of our neural networks, and the hormones that are involved in feeling hungry. And so from a central perspective, from a brain perspective, these drugs help us to also feel less hungry, not just because it's slowing down digestion, but it's also modifying hormones that are involved in the hunger sensation, and they also help to break that kind of food reward pattern. 

In other words, you'll hear many people who are taking these drugs will say that food doesn't bring them the same kind of comfort, or even joy, that it used to, and that, for some people, is very helpful, who are trying to, or struggling with, this constant desire to eat food. These drugs can help to reduce that desire. 

Jamie DePolo: So, it's almost, if I'm understanding you correctly, it's kind of retraining your brain, like the way you think about food, and the way you think about being full. Am I understanding that right? 

Dr. Neil Iyengar: I think that's a good way of putting it. I would make one very small nuance change to the way that you've phrased it. I think it's a good way of phrasing it, but I wish it was retraining the brain. The problem is, when you stop these drugs, a lot of the original effects, or a lot of those effects go away, and the original hunger returns, and so forth. So, it's not necessarily a retraining where you would anticipate those are long-term effects, even off the drug. It's essentially, I guess, a temporary state, induced by the drug. 

Jamie DePolo: Okay, so it's sort of changing the brain chemistry, so you feel differently, and think differently, then when you stop taking it, that change in brain chemistry goes away, as well. 

Dr. Neil Iyengar: Yeah. 

Jamie DePolo: Okay, okay. Now breast cancer is considered a weight-related cancer, because people, especially women, who are most of the people that get breast cancer, with excess weight, have a higher risk of developing the disease. And if somebody has been diagnosed, excess weight ups the risk of recurrence. 

So, what do we know, if anything, about the safety of GLP-1 drugs for people who are receiving breast cancer treatment, or if you know they have a history of it, and maybe they're done with active treatment? 

Dr. Neil Iyengar: Yeah. So, I think that's a very important question, right? And I would kind of approach this from the first piece that you mentioned, and that's the breast cancer risk perspective. You know, in that setting, for people who have not been diagnosed with breast cancer, but are worried about their breast cancer risk, that's where, as you mentioned, body mass index, or your fat tissue levels, or your body weight, can contribute to the risk of developing breast cancer. And there, it looks like it's mainly post-menopausal breast cancer. Having a higher weight increases the risk of developing breast cancer after menopause. 

For pre-menopausal women, there does not seem to be an increased risk of developing breast cancer, pre-menopausal breast cancer, with increased weight, and so that is, you know, a whole other conversation, we could have. But you know, I think certainly, for preventing post-menopausal breast cancer, which is the most common type of breast cancer, there's a lot of interest in whether or not we can use these weight loss medications to lower post-menopausal breast cancer risk, although that's not been definitively shown yet.

In that setting, I'm less concerned about safety, because you're not on cancer therapies. And in fact, these drugs have shown to have many other positive effects in terms of cardiometabolic health, and improving overall lifespan, because of improving cardiometabolic health. 

Now, in the post-cancer diagnosis setting, as you raised, that's of course, a whole different issue. And in somebody who's been diagnosed with cancer, and let's say breast cancer, specifically, I think we certainly need more data and studies to tell us about the safety and potential interaction of these drugs with breast cancer therapies.

I would say with chemotherapy, for example, we have little to no data to tell us about the safety of combining these. We have some retrospective, or observational studies, that have looked at how patients and people have fared when they're on these treatments together, but I would worry about whether or not the combination of these therapies — breast cancer therapy and weight loss therapies — could accentuate some of the side effects, particularly with chemotherapy.

At the beginning, you mentioned nausea, and different types of bowel effects, constipation, even diarrhea, and we know that chemotherapy can do a lot of that, as well. So, in the setting where somebody's getting chemotherapy to treat their breast cancer, getting the appropriate doses and schedule of chemotherapy is the first priority. And so, I would be concerned that if you add on a weight-loss drug and it could accentuate some of those side effects, and potentially, disrupt the ability to give the optimal course of chemotherapy. 

Now for other types of breast cancer treatment, we are in a similar boat. So immune therapy, we don't have much data about interactions, and again, the side effects could mount up. We do have more data about using these drugs, the weight loss drugs, while women are on hormone therapy. 

Jamie DePolo: That's what I'm most interested in, because that's, you know, that can be a five- to 10-year commitment after chemotherapy, surgery, radiation, if someone has to have those particular treatments. And so, that's where I can see people like, hey, you know tamoxifen, I gained some weight. What about one of these drugs? 

Dr. Neil Iyengar: Yeah, yeah. And so, that's a great question. And that's where I think we do struggle, the most, with weight change, right? We know that hormone therapy, a lot of women on hormone therapy, as you mentioned, gain weight. We also know from clinical trials that weight gain can reduce the effectiveness of some hormone therapies, particularly aromatase inhibitors. And we also know that weight gain, typically more than 10% of what your weight was at the time of breast cancer diagnosis, can increase the risk of breast cancer recurrence. And so, certainly, stopping weight gain, or even inducing weight loss, could potentially be helpful, both from the perspective of keeping people on their hormone therapy. You know, I have many patients who get so fed up with the weight gain that ultimately, they either discontinue their hormone therapy or they switch to less effective hormone therapy. So that's a big issue. 

And then, of course, using these drugs to reduce the risk of breast cancer recurrence is of great interest. But we don't have any clinical trial data, yet, to answer those questions. We do have some observational data sets, which have looked at women who have been on hormone therapy and who've decided to take a weight loss drug, a GLP-1 receptor agonist, and we have some data sets that our group published from Sloan Kettering. We also have, probably, the largest data set so far, from MD Anderson, and some other smaller data sets from Yale and Cleveland Clinic, and others, and Ohio State, and others. And if we put all that together, what we generally see is that the amount of weight loss that women on hormone therapy for breast cancer who are taking the GLP-1 receptor agonists experience, is less than what has been reported with the use of these weight loss drugs in the general population. In other words, in women who are not on hormone therapy. 

That being said, there still, generally, is weight loss. It's usually somewhere between 3% to 5%. Now contrast that to the 10% to 15% range that is seen in populations without cancer. And so, I think that we are learning about the interactions of these drugs with cancer therapies and hormone therapies. Right now, I don't see any major concerns for safety interactions with hormone therapy, unlike what I outlined with chemotherapy and immune therapy, but I think we have a lot to learn in terms of what is the right dose of the weight loss drugs, what's the right duration of the weight loss drugs? And we have little to no data on the long-term effects of these drugs in women or men with cancer or cancer survivors.

Jamie DePolo: Right. Well, thank you for that. And it's interesting, too, because there was just a story that I read that was looking at real-world, in the real world when people were taking either Wegovy or Zepbound, that they were losing a lot less weight than the clinical trial showed. So, it sounds like that's kind of paralleling what you're seeing in women on hormonal therapy. And that, also, interestingly, when the people stopped taking the medicines, or took a lower maintenance dose than they were technically prescribed, they didn't gain as much weight back. 

So, it sounds like both sides of the coin are a little bit less than the clinical trials showed. Would there be a reason for that? Because it's not quite so structured? Is that perhaps one reason? 

Dr. Neil Iyengar: Yeah. You know, I think that weight loss can be a double-edged sword in a couple of ways. And what I mean by that is, the more weight loss a person experiences, the higher the risk of having that kind of yo-yo effect, where whatever you're doing that's inducing that weight loss, once you stop it, now, you're more vulnerable to larger amounts of weight gain, if you had larger amounts of weight loss. 

So, that's what I suspect is being reflected in that study, is that patients lost, maybe less weight than what was previously reported, and so there was less weight to put back on once they stopped the drug.

But it does raise important questions, and sort of what I was alluding to earlier about, what are the appropriate dosing strategies? And this is very important, particularly, to people who are dealing with a cancer diagnosis, where we do not want the weight to yo-yo like that. That can have some even worse implications, potentially, for the cancer than remaining weight-stable. And so we need to learn more about what's the optimal dose, duration, and then, can we use maintenance doses of these drugs? Can we pulse them on and off to help people with their overall weight journey?

Jamie DePolo: Okay, thank you. Now, the European Congress on Obesity 2025 meeting, some researchers presented a study showing that these medicines had anti-cancer benefits beyond weight loss. And when people asked why, it was like, oh, we're not really sure. Is there any sense of what might be going on in there? Is it hormonal? Or do we know? 

Dr. Neil Iyengar: Yeah. It's a great question, and I do think the jury is still out on this one. And it probably varies by cancer type, and the types of treatments that have been used for that cancer. But there have been some interesting preliminary data, which might suggest that there's something more than just weight loss which could contribute to a beneficial effect of these drugs on cancer. 

And so, for example, there are some data in animals that suggest that these drugs can modify our immune response in a favorable way. But what we really don't know is, is it a favorable modification when you're using immunotherapy? The types of responses that we want to induce may not be the types of responses that somebody getting immunotherapy would want. 

And so, again, there's a lot that we don't know. But what I would say is, I'm not yet convinced that these drugs have anti-cancer effects beyond just the weight loss. And I say that because there have now been at least two studies — and these were in mouse models — and essentially, what they did was they took models, or animals, that had breast cancer. And in one group, they gave them the weight loss drugs, and in the other group, they calorie restricted the diet, so that they were eating the same amount of food as the mice who were being treated with the weight loss drugs. And it turns out that both approaches led to decreased size of the tumors, but equivalently. And so what that tells us is that it really doesn't matter, at least in those experiments, how you lose the weight. It's the weight loss itself that contributed to the reduction in tumor size. 

Now that being said, when you look at metabolic markers like glucose, insulin, and leptin, and other hormones that have been associated with breast cancer prognosis, the best effects on those hormones in those animal studies, actually came from calorie restriction and not from the weight loss drugs, interestingly.

I think the jury's still out on the question that you asked. I'm not sure that they directly have anti-cancer benefits and it also tells me that we need to be using both lifestyle modification and these drugs, for those who choose to use them. 

Jamie DePolo: Oh, that's very interesting. Thank you. 

Now I feel like the benefits of these drugs are so well known. I mean, the commercials are everywhere. I feel like if somebody is not on them, they have at least two or three friends who are on them. So I'd like to talk a little bit about the risks and the limitations. 

I know in many cases people lose muscle mass, which is concerning. And also, while people may lose weight when they start taking the drugs, from what I've read, then the weight kind of plateaus. So, they don't continually lose and if they stop taking the drugs, as we discussed earlier, you know, they gain the weight back. And then I've read also extreme fatigue, bone loss, which is a big issue for post-menopausal women, or you know, people on hormonal therapy. And then, abdominal pain is also another side effect. And then, there was a study that came out last week that suggested that people who were taking the medicines for diabetes had a higher risk of age-related macular degeneration, which can lead to blindness. And then I think this was in the UK, the regulatory agency reiterated that women using these weight loss drugs have to use safe and effective contraception because nobody really has any idea how this affects an unborn baby. 

So, I know there hasn't been a lot of research. Are we concerned about the long-term side effects of these drugs? I mean a lot of people do seem to be on them. So, I'm just curious, are we going to see some things 10, 15, years down the road? 

Dr. Neil Iyengar: Yeah, well, thank you for highlighting all of those concerns. Those are my concerns, as well. 

So it's a real issue. However, that being said, you know, I think that, and you alluded to the benefits being well known, and they are, I think, for most patients that meet the indication for these drugs that, in other words, would have qualified for the clinical trials through which these drugs were approved, most of those folks derive benefit and the benefit outweighs those risks. 

And those benefits, of course, are the weight loss benefits we were talking about, but really the reduction in cardiometabolic events, the reduction in heart attacks, the reduction in diabetes complications. And we know that breast cancer survivors have more than a doubling in their risk of developing diabetes or other cardiometabolic disorders after breast cancer treatment. 

And so, I think that for patients that have major metabolic risk factors — obesity, insulin resistance, pre-diabetes — those are the folks who are most likely to derive more benefit than harm from these drugs. 

However, the harms are something that we really do need to address. And for me, the way that I would prioritize them are, One: the loss of lean mass is a major concern for people with cancer because our lean mass is so important for our functional status, for our insulin signaling, and for so much more in cancer outcomes. There have now been plenty of studies showing that low muscle mass corresponds to worse survival and higher risk of recurrence, and so forth, for those people that have been diagnosed with cancer. So, if you have a drug that's doing this, that would be a major problem. Now the question is, can we pair that with exercise, and nutritional changes that could help to avert that loss of lean mass?

The other concern, of course, is something we talked about earlier, is exacerbation of side effects. If this is causing somebody abdominal pain, is that going to make it harder for them to take their Verzenio or CDK4/6 inhibitor, their hormone therapy, which also causes abdominal pain and diarrhea, right? And so, that is a major concern. 

The next concern is, I would say, the potential yo-yoing effect that we talked about. What happens when you stop these drugs? And again, for patients with cancer, it's a greater concern if the weight is going up and down and up and down, rather than being more stable. 

And then, lastly, I would also bring up some of the mental or potential psychological effects. And I think this is particularly important for people dealing with a cancer diagnosis. We talked about this earlier, but one of the ways that these weight loss drugs work is, essentially, through reducing our craving or desire for food. And for people who have the joy of eating, or get joy from consuming foods, now there's a fine line, you can also have emotional eating, and have some degree of emotional dependence on eating, and eating can be a method of avoidance for other issues in one's life. But this is all interweaved, and then made worse by a cancer diagnosis. 

And so one of the things that I tell my own patients is that if you are planning to embark on a weight loss therapy with one of these medications, I would definitely get a therapist, or psychologist, or psychiatrist involved as part of your care team, because you don't want to be in a situation where you've eliminated one of your sources of joy, or even you've eliminated an emotional coping mechanism, albeit not the healthiest. But you don't have a strategy for something to recover from that emotional crutch. 

And so, that's something that is also an important piece of the discussion.

Jamie DePolo: That makes sense. Practically, as a doctor, there are so many of these drugs. If one of your patients came to you, someone you care for, and said, okay, you know, I really would like to do this. How do people decide which one is the best? As far as I know, only, I think only two of them have been compared head-to-head. And they all seem to work the same. I don't know. I don't know the ins and outs, but how do you decide? 

Dr. Neil Iyengar: Yeah, it's a great question. So, we don't know, from a scientific perspective, especially if there's one that's better than the other when somebody is dealing with a cancer diagnosis. But my general approach is, and you know, just to be clear, overall, I think that these drugs are actually phenomenal tools for managing weight and for managing metabolic health. 

And so I have many patients who are taking them, and I think that, you know, we're currently in a setting where you've got this potentially great tool, but we've got limited data. So we have to walk this fine line of, what's the safest way of using these medications? And in some ways, for some people who have high metabolic risk, there's risk to not using these medications. And that goes back to what we were talking about earlier, about weight gain being associated with cardiometabolic disorders and cancer recurrence. 

So my general approach is, I do not favor starting these drugs if somebody is on chemotherapy, and I generally, try not to start them if somebody is on immunotherapy, or a CDK4/6 inhibitor like Verzenio or Kisqali, which we're now using in the adjuvant or early-stage setting.

If somebody is on observation or is on hormone therapy and has been stable on hormone therapy, then I think those are settings where these drugs are likely to be the most beneficial, and will introduce it then.

And I collaborate, generally, very closely with either a weight loss specialist or an endocrinologist because I do think that the way that you titrate, or you dose these drugs, needs to be very closely followed, especially in somebody who is a cancer survivor or who's on cancer treatment, like hormone therapy. And that gets to you want to start backing off on the dose once you've achieved the goal weight loss. You don't want to lose too much weight because, again, we don't want to induce too much lean mass loss. 

So, it's important that if you start one of these drugs, you do it, of course, after discussion with your oncologist, usually best with an involvement of an endocrinologist or weight loss specialist. And to make sure that you're doing it with appropriate lifestyle modifications, and we can get into what that could be. But lifestyle modifications to try and mitigate the effects on lean mass and on bone. Keep a goal weight loss in mind and be ready to back off on the dose or even stop the drug once you've achieved that goal weight loss. You don't want to go in with the philosophy of, I'm going to get as much as I can or keep pushing it, because that can be dangerous. 

And then, as I mentioned earlier, involve a mental health professional in your care team when starting these drugs. 

Jamie DePolo: And before we get to the lifestyle modifications you mentioned, I'm wondering if somebody does have, say, very troubling side effects from one of these medicines, like say, they start out, Wegovy and just constipated or diarrhea, something like that. Can they switch to another one? Are they interchangeable like that? 

Dr. Neil Iyengar: Yes, you can switch. And some of these medications, some of them have more GI — gastrointestinal — side effects than others. So, a successful strategy can be to switch from one to another. Dietary modification can also help with the GI side effects. And then, you know, we also have to keep in mind that within this class of drugs, there are your dual agonists, there are your single agonists, and your triple agonists. 

So, some of the original versions of these drugs were single receptor agonists, meaning that they stimulate just the GLP-1 receptor. But we now have GLP-1 and GIP agonists — dual agonists — that agonize both of those receptors. And there are triple agonists that are coming down the pipeline as well. 

The dual agonists, for example, tirzepatide, has been shown to induce more weight loss than the single agonists, the GLP-1 receptor agonist, for example, semaglutide. Now, whether the dual or the single or the triple agonists are better for people who've been diagnosed with cancer, that we really do not know. And so, that is another area where we need more data. 

Jamie DePolo: Okay. And then, you talked about the lifestyle modifications. I'm assuming that would be diet and exercise? 

Dr. Neil Iyengar: Right. That's right. You know, I think that one of the important things about lifestyle modification with these drugs, as we've been talking about, is you want to be ready for the goal, or maintenance phase. A lot of folks will jump into medical weight loss therapy without really thinking about, okay, what am I going to do once I hit my target weight? And it's important to set that plan up right away, right from the get-go. Because it can be a real challenge once you get there, and you stop the drugs, and the cravings come back, and everything comes back. It can be real challenging if you enter that phase without a plan. 

So, if you are instituting lifestyle changes when you start the drugs, and that's eating healthy, and that's exercising, both aerobic and resistance training, then that'll set you up for success, because if you can get into a routine, and you can then maintain that routine, you've trained yourself, going back to the training idea, you've trained yourself to do all of that. It'll still be challenging when you stop the drugs, but at least you have some amount of routine and a plan to keep in place. That's the number one goal of instituting lifestyle changes.

The next is maintenance, or improvement, of lean mass. And this is where your protein-to-carbohydrate ratio can come into play. Eating more protein. The levels of protein consumption for people who are trying to put on muscle tends to be a bit higher than those who are wanting to maintain muscle mass. And there we say anywhere from 1 to as high as 1.5 grams of protein per pound, per day, to increase your muscle mass. 

And then the other piece is a high-fiber diet. And that's important for the GI side effects, but also, in cancer in general, we have data to suggest that a high-fiber diet can be protective against cancer progression or recurrence. 

And so even apart from these drugs, I generally advocate for a high-fiber diet that's 20 to 30 grams, at least 20 to 30 grams of fiber per day. And certainly with these drugs, that becomes even more important. 

And then, of course, the exercise piece, both for increasing or maintaining lean mass, but also weight-bearing exercise, to maintain your bone density, as well. 

Jamie DePolo: I have a question. Well, I have three more questions. But the first one is, when you talk about 20 to 30 grams of fiber per day, could you put that like, is that a bowl of broccoli? What is that in, in an actual portion size?

Dr. Neil Iyengar: It is, unfortunately, a lot more than a bowl of broccoli. It can be a real challenge to get that much fiber. The average American gets about 8 to 10 grams of fiber per day in their diet. So, we're talking about tripling, essentially, doubling to tripling, the amount of fiber that the average American is getting in their diet. 

And this is where, if you follow the guidelines of eating a serving, at least one serving of vegetables with every meal, that will help you achieve the fiber goal. I tend to recommend nutrient-dense, plant forward-based diet. So, there are a lot of legumes that are great sources of both protein and fiber. Navy beans, for example, is a source of both. 

Editor’s note: One cup of boiled lentils has about 15 grams of fiber. One cup of chopped boiled broccoli has about 5 grams of fiber.

And then I'm generally not a fan of nutrition supplementation, but fiber is one of those areas where, if you need a little bit extra after making those dietary changes, adding some fiber supplementation can be helpful, too. 

Jamie DePolo: Okay. And then, from what I've read, and again, I'm not the scientist, but it sounds like people, they take these drugs, they may achieve their goal weight, and then they kind of go on a maintenance dose or do they stop? So, I guess I'm a little unclear on how that works.

Dr. Neil Iyengar: Yeah, and I think that's because the field is evolving. Both the weight loss field, but also the questions of, what do we do in the context of a cancer diagnosis? And I think ultimately, we know that the amount of weight loss is dose-responsive. It depends on the dose. And so, if you're not getting enough weight loss, typically increasing the dose will increase the amount of weight loss. It could potentially increase the amount of side effects, as well. So that's something to watch out for. And then, if you've reached your goal weight, or if you're losing weight too rapidly, then backing off on the dose is important as well. 

And then ultimately, that maintenance setting, I think a lot of folks do actually want to come off the drug, so that they're not, you know, dependent on it. And I'm not using dependent in the medical sense, where you have a bodily, physiologic dependence on the drug. But you know, a lot of folks understandably don't want to be on long-term medications or yet another long-term medication. 

So, I think it is a very reasonable goal to come off the drug entirely, if you can maintain weight with the lifestyle changes. But as we've been talking about, that can be a real challenge and that's where the concept of a maintenance dose has been interesting and attractive. It's just that we haven't yet gotten to a standard practice for who should be pursuing a maintenance dose, what the maintenance dose is.

I've even heard in online forums that people are micro-dosing these drugs. So, you know, I think everybody is sort of coming up with their own creative solution in terms of what to do once they reach their goal weight loss. And my opinion is, right now, the best approach is to try to prepare yourself for that maintenance phase by using lifestyle modification, so that you can try, and entirely come off the drugs. And then maybe pulse the drug back on if you start to struggle with weight gain, significant weight gain again. But I am very intrigued by some of the ongoing research in terms of maintenance dosing. 

Jamie DePolo: Okay, thank you. And then my final question is a little bit of a tangent, but I was just at the ASCO annual meeting and researchers from Canada presented the results of the CHALLENGE trial, which to me, it was fascinating. So they randomized a group of — and this was in colon cancer, not breast cancer — but a group of stage III colon cancer, people with stage III colon cancer who had completed chemotherapy. And they either did a three-year structured exercise program, or I believe they just got handouts on how great exercise is for you. And what they found was that the people who exercised had better overall survival and better progression-free survival, whether or not they lost weight. Which to me, was fascinating. And so I'm wondering how that kind of fits in with all of this, especially, considering the mouse study that you talked about where, you know, the mice who lost the weight had the better markers and the tumor shrunk. 

So can you help me make sense of all this? 

Dr. Neil Iyengar: Yeah, absolutely. I think that one of the things that I like to say is that lifestyle interventions, like exercise, like structured exercise interventions, and dietary interventions, these are powerful tools and we can use them like medicines. We can dose exercise. We can give exercise prescriptions. Same for diet and nutrition. And in a lot of the clinical trials that my group is doing, we are testing what we call precision lifestyle interventions, where you dose them. 

And so in that same concept, we can use lifestyle interventions for different indications, just like we do medications. And so when I go to my exercise physiology team, and I say, I have a patient who we want to design an exercise prescription for, you know, one of their first questions is, well, what are the goals here? And if weight loss is one of the goals, then the exercise prescription is designed a little differently to emphasize energy expenditure. Whereas if weight loss is not a goal, let's say the person has a normal weight BMI, and the goal really is to improve their cardiorespiratory fitness, then the prescription is going to look a little bit different. 

So ultimately, we know from now a large body of research, that exercise seems to have protective effects against cancer that are totally independent of its use for weight loss. Exercise can improve oxygenation. Exercise can improve anti-tumor immunity. Exercise can improve a lot of symptoms that are associated with cancer and cancer treatment. So that can make people feel better and perhaps more adherent to their treatment. 

So there are a lot of effects of exercise that are totally independent of weight loss. And I think that is essentially what we're seeing in the CHELLENGE trial, is that it was not designed as a weight loss intervention, but rather as an exercise intervention, with the goal of improving function and fitness. And there, that trial is so important because it really shows us that the protective anti-cancer effects of exercise can translate, when implemented appropriately, can translate to reductions in cancer recurrence and improvements in survival. 

I just want to make the point, though, that it's really important to note here that the trial was not designed to show that you can replace standard cancer therapies with exercise, but rather, you can augment and improve outcomes when you add exercise to standard cancer therapy. 

Jamie DePolo: Yes, absolutely. Thank you, for pointing that out, because yes, the people had chemotherapy and then this was kind of after.

Dr. Iyengar, thank you so much. This has been so helpful. I've learned so much. I really appreciate all your insights and you taking the time to talk to us today. 

Dr. Neil Iyengar: It's been my pleasure. Thank you for having me on.

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