The Importance of Diet and Exercise in Cancer Survivorship

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Ann H. Partridge, MD, MPH: Hello. I’m Dr Ann Partridge, and welcome to season 2 of the Medscape InDiscussion podcast series on cancer survivorship. Today, we’ll discuss diet and exercise after cancer treatment and actually during cancer treatment as applicable. This is one of the hottest topics and one of the most frequently asked questions of my patients when they’re diagnosed and in survivorship.

But first let me introduce my guest, Dr Melinda Irwin. Dr Irwin is the Susan Dwight Bliss Professor of Epidemiology and Associate Dean of Research at the Yale School of Public Health. She’s Deputy Director of the Yale Cancer Center and Deputy Director of Public Health in the Yale Center for Clinical Investigation.

Nationally, Dr Irwin co leads the Southwest Oncology Group (SWOG) Cancer Research Network Cancer Survivorship Committee. In 2018, Dr Irwin completed an executive leadership in academic medicine program, and she’s a leader in academic medicine through and through.

Her experience working across departments, schools, and with interdisciplinary groups of investigators, particularly around the subject that we’re about to talk about, has provided her with the skills to train and mentor many people effectively, including me and those listening to us today. Welcome to the Medscape InDiscussion: Cancer Survivorship podcast.

Melinda Irwin, PhD, MPH: Thank you for inviting me to discuss this topic.

Partridge: We’re so happy to have you. You’re really a maven in the field. You’ve been doing this for a long time. You’re focused on this topic and you’ve really helped us to learn more about this. What got you interested in this particular topic?

Irwin: Throughout my childhood, I was a competitive athlete and with that comes many injuries. I was a frequent visitor to the orthopedist. I had knee surgeries and whatnot. With my involvement in sports and medicine indirectly, I always thought I would go into orthopedics. But then in high school, my mom was diagnosed with breast cancer.

This was in the mid-80s, and she was in her young forties, and it really kind of rocked my world. It was at a time completely different than now, where no one talked about cancer. In fact, after her diagnosis, I was sort of told to keep it quiet. There wasn’t the internet or websites or support groups online and whatnot. There was definitely no information around how to prevent cancer through lifestyle behaviors.

When I went to college, I sort of pivoted and wanted to focus on prevention and on the role of nutrition, exercise, and weight. That then led me to graduate school, focusing on epidemiology at the population level and how we prevent disease, which led to a postdoc fellowship as well, learning more about clinical trials for cancer prevention.

And now, decades later, at Yale, in the School of Public Health and the Cancer Center, I just feel so lucky to do the research that I do with so much research really supporting the role of lifestyle behaviors in preventing and improving cancer outcomes.

Partridge: That’s a great origin story. You lived the lifestyle, and now you’re trying to study how it can be preventative of primary and secondary cancers, right? So what do we know when we’re talking about all cancer, specific cancers, where does lifestyle and diet and exercise specifically matter, and where might it not matter as much?

Irwin: We know that about 50% of cancers can be prevented, whether that’s through tobacco control, vaccines but also through lifestyle factors such as weight, diet and exercise. Specifically talking about lifestyle behaviors, we know there’s about 14 different cancers associated with weight, physical activity, and diet.

Much of the research has been done in breast cancer and colorectal cancer, primarily because those are the most common cancers and, to enroll patients into trials, some of the first studies were among those. But now, there is a growing body of literature in ovarian, endometrial, esophageal, and lung cancer as well.

So the benefits of these lifestyle factors on numerous different outcomes, whether they’re patient reported outcomes or clinical outcomes is just growing.

Partridge: And it’s not just about preventing heart disease because many people are going to survive through it. It’s actually cancer-specific recurrence and survival, correct?

Irwin: Yes. For example, the Diabetes Prevention Program (DPP) was a seminal study published in The New England Journal of Medicine in 2002, really showing the benefit of lifestyle, diet, and exercise compared to metformin compared to usual care on preventing diabetes. That DPP program has now been used in similar trials in the cancer setting.

In much of the work I do, we adapt the DPP to a specific cancer patient population and intervene and look at outcomes. While there’s been so much observational prospective cohort studies, hundreds of studies showing higher weight, worse cancer mortality, improved diet quality, higher physical activity, and lower cancer mortality; there actually are a few definitive randomized control trials to date looking at randomizing people with cancer either at onset or shortly after treatment is complete, randomized to an intervention vs control on disease-free survival. As you know, the Breast Cancer Weight Loss (BWEL) trial led by Jen Ligibel and you and many others are involved, will be coming out in a couple of years. This trial is focused on women with breast cancer, looking at a lifestyle intervention vs control.

There are other trials in colon and ovarian cancer. I think in the next 2-3 years, we’ll have this definitive research of lifestyle interventions on survival and recurrence. But to date, we have many trials looking at biologic or surrogate marker endpoints, such as inflammation and metabolic markers, that we know increase our risk of developing or dying of cancer. The thought is that if these interventions are improving those intermediate surrogate markers, then they must improve recurrence and mortality.

Partridge: I just want to pick up on the intermediate surrogate markers and ask what is in my mind, the holy grail question, which is what’s our inkling of why or how diet and exercise or energy balance might have an impact on cancer outcomes.

Obviously, the goal would be not just to get people to exercise and diet, like we’ve talked about, but to kind of bottle it. Whatever that mechanism is, can we put it in a pill or administer intravenously and get it to the patients who can’t otherwise diet or exercise? What do we think? What are the best scientific hunches right now based on the evidence?

Irwin: Many of the biologic markers, these intermediate markers, whether it’s insulin or inflammation, say C-reactive protein, we know increase cell proliferation, which then can lead to downstream adverse effects. When we look upstream to what’s causing the sort of chronic inflammation systemically in our bodies that leads to weight gain and then obesity, the major upstream factors are our toxic food environment and the fact that we’re all inactive because of our devices, on our iPhones, and on our computers. But by eating a poor diet, that increases our glucose and our insulin levels; there are so many mechanisms that lead to insulin resistance, that then lead to inflammation, that lead to adverse changes in estrogens, and then that leads to the downstream factors. It’s very clear the mechanisms and how it works. There’s even more clarity now that treatment works. We’re living in this sort of [semaglutide] craze, right? Where there are a demand by people to take medications to elicit weight loss. There’s so much evidence showing that this is now leading to improvements in diabetes, heart disease, and even cancer. But I think what’s less known and what is really important to me is how we prevent obesity. How do we prevent a poor diet and inactivity?

My concern is that we as a society are setting people up to take medications for life. How can we prevent that? How can we prevent a society where it will just come to a point where people are taking medications? I think that really gets to the crux of it, which is that system-level changes are needed in how we refer patients or what are we referring them to. At the end of the day, we know people want this information. There’s overwhelming information that a majority — 80% or more of people — want information on nutrition and exercise, healthy eating, weight management for cancer prevention, control, as well as other disease outcomes.

Partridge: Do we already have data that the glucagon-like inhibitor peptide 1 (GLP-1) receptor agonist inhibitor weight loss is associated with cancer outcomes? I know weight loss and gastric bypass and the like has been associated with fewer cancers being diagnosed.

Irwin: Most recently at American Society of Clinical Oncology (ASCO) in 2024, there was a retrospective. These are not prospective randomized controlled randomizing people to taking a medication or surgery or lifestyle intervention, but from retrospective analyses and there are limitations with that. Comparing bariatric surgery to anti-obesity medications, there were improvements on cancer outcomes. Bariatric surgery led to more weight loss, but the outcomes were actually improved with the GLP-1s. There could be other issues just because it wasn’t set up prospectively as a randomized controlled trial, but I think it’s provocative nonetheless. There are other observational findings. And the strength of this research with bariatric surgery and GLP-1s is the effect size, the amount of weight lost, in turn, is showing large improvements in a whole host of clinical outcomes. With lifestyle interventions such as healthy eating and exercise, we’re not necessarily going to see a 25% weight loss, maybe a 5% weight loss and a maintenance of that 5% weight loss, and that’s clinically meaningful.

So I think we’re at a good place where people can have more choices as to what they want to do. As you know, with the GLP-1s, they have to take these medications for life. If they stop taking them, they’ll regain the weight. I think there’s an opportunity here to continue to focus on treatment. But we also have to make sure we’re focusing on prevention, preventing weight gain, and preventing people from becoming inactive.

Partridge: That’s really helpful and hot off the presses from ASCO. Thank you for that. I was not aware of that abstract. Hopefully, it will make it through peer review, and we’ll see what comes out in the presentation or the publication.

So, you’ve got a cancer survivor, they ask for — or you hopefully proactively give them — the information that we have. You give them the recommendations. They’re an average breast cancer survivor and they’re less active than they’d like to be. They’re busy, work gets in the way. Now, their cancer treatment has gotten in the way. Their life is in a little bit of disarray as they try and recover from what I call the aftermath of cancer treatment.

Let’s say they’re on their hormones, and they gained a little weight with chemotherapy. What kinds of things are we going to say to that person? How do we say it and then help them effectively change their behavior?

Irwin: Those are all really important questions. I think the current approach that is taken — at Yale and many cancer centers and cancer hospitals — is an opt-in approach where the oncologist or the surgeon or whomever tells the patient maybe of a supportive care service if the patient asks.

I think it would be great if we had an opt out approach where every single patient at diagnosis is provided this information and automatically referred to — whether it’s a survivorship program or clinic or some supportive care service — and it even could be à la carte, but they have to be presented with the information, whether it’s through educational information and a brief 5-minute discussion with the provider. But that referral has to occur to an evidence-based supportive-care program. I think it’s important to start this at diagnosis or, for example, if they’re having chemotherapy and they have a chemo teach before they’re beginning, that’s a good opportunity to talk about some of the side effects of chemotherapy and use that as an opportunity to talk about the services available, including seeing a registered dietician. Most cancer hospitals have dieticians on board, many of them there, but the referral is low. There’s a lot of malnutrition with certain cancers, including head and neck and esophageal cancer and whatnot. So I think we have to switch the approach from this opt in to this opt out and start it early at diagnosis.

We have two trials, one that just completed. The LEANer trial that was in women with breast cancer that started at diagnosis and randomized women during chemotherapy to a lifestyle intervention of nutrition and exercise vs usual care. We have a trial in progress in women with ovarian cancer initiating chemotherapy. In both of those trials, when the women finish those who were randomized to intervention, they are so appreciative of this information and the support they were given on how to eat a high-quality diet while they’re facing nutrition impact symptoms from the chemotherapy and how to maintain their muscle mass, knowing the importance of muscle and sarcopenia and whatnot. Very few have finished the intervention and were upset that they had it. I think if we start early, there’s only benefits.

Partridge: I put people on that trial, and I think it’s exciting because you are looking at tolerance as well as getting through the chemotherapy, correct? Adherence to their chemotherapy. I think that’ll be very telling. If the data show us from that trial, that it helps people get through their treatment and they tolerate it better, then shame on us if we don’t incorporate it into their teaching, like giving people anti-nausea medications when they need it to get through their chemo.

Irwin: Yeah. And we understand why it’s easy to give a prescription, right? It doesn’t take but a minute to write it out, and it’s easier for patients, perhaps, to just go fill it take it. But I think we can do better. We have to do better. What concerns me is we have another study we did in our sample of women enrolled in our trials, it’s about a sample of about 500 women; 80% of them were taking dietary supplements. These supplements could have toxic effects, for example, with endocrine therapy or even chemotherapy. They’re taking these dietary supplements because they think it will help them, right? We need to provide counseling and support to direct them based on evidence, based on our guidelines. We have ASCO guidelines on this. But it’s kind of wrong of us to assume that they don’t want this information. They do. So I think in turn, the system has to sort of shift to allow for this space. Also going back to medications, especially with the GLP-1 inhibitors, we know that in any kind of advancement in treatment, there’s worsening disparities. The cost of these medications is close to $1000 a month. Who is taking these medications, and who is not able to take these medications? At a minimum, we need a good baseline, and that baseline has to be, at a minimum, very good referral to evidence-based nutrition and exercise counseling and weight management. I think we can do that. I think the system can handle that.

Partridge: So if I see a survivor, they’re listening to me, and they seem engaged. I’ve done this proactively. I mention a plant-based diet, and I want you to increase your steps and get the 150 minutes of moderate activity a week. It doesn’t have to be a marathon. I’ve got my whole spiel. How do I do that to make sure that they can hear me? Then how do I handle it when they tell me that, you know, they don’t have a grocery store with fresh vegetables anywhere near their home? Obviously, that leads to the structural disparities that we have in many parts of the world.

Irwin: First off, I think if we tell the patient everything you just said, like you got to do this, you got to get off this. It’s too much. It’s too overwhelming. I think we have to meet the patient where they’re at.

Our first question has to elicit from them what change do they want to make? Maybe focus on just one change to not overwhelm them with all the recommendations. They might want to focus more at the beginning on reducing sedentary behavior. If they have an iPhone, it’s easy for them to look at the heart app and give them a goal of trying to increase a thousand steps per day. If they’re having chemotherapy, time it so that maybe 2-3 days after their infusion, they can really start to increase their steps. If diet is easier for them, focus on one aspect with diet. Maybe they’re drinking sugar sweetened beverages so focus on how to reduce that.

I think meeting the patient where they’re at is critical and starting with one or two behavior changes. But what’s also important is as an oncologist or surgeon, you can give a small, short 1- to 2-minute talk and do a referral. But I think what your point is, you do the referral, but how can you make sure they’re going to follow through with that and get something out of that session with the dietician or the exercise physiologist.

This is behavioral science, right? I think by starting with the patient, there’s a lot of publications on the five As, on that approach of asking and how to get them to achieve behavior change.

Partridge: I love it. You always do teach me things. So meet the patient where they are and try one to two things over time as opposed to overwhelming them with my full spiel. Right?

Irwin: I think so. Think about what works for us, right? There are days where we just want to binge on a Netflix series, and that’s okay if you have a Saturday or Sunday that you’re doing that. Dieticians that I’m lucky to collaborate with have this 80% rule, like try to be healthy 80% of the week, right? And then, give yourself a break 20% of the week.

Partridge: That’s fantastic. Today we’ve talked with Melinda Irwin. Melinda, you are terrific as expected. Key takeaways are meet the patient where they are and change maybe one to two things at a time. Some change is better than none. I think we can really help our patients and to plug them in with the resources in your environment, at your cancer center, in your community.

Thanks to all of you for tuning in. Please take a moment to download the Medscape app to listen and subscribe to this podcast series on cancer survivorship. This is Dr Ann Partridge for the Medscape InDiscussion: Cancer Survivorship podcast.

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