Incorporating the Emerging Field of Exercise Oncology into Breast Cancer Care

Neil M. Iyengar, MD

Memorial Sloan Kettering Cancer Center

Co-Editor-in-Chief of ONCOLOGY^®

Combining the interaction with patients and a love for biology and physiology led Neil M. Iyengar, MD, to decide on a career as a breast oncologist.

In a discussion with CancerNetwork^®, Iyengar, associate attending physician at Memorial Sloan Kettering Cancer Center, and co-editor-in-chief of ONCOLOGY^® spoke about some of his proudest career accomplishments surrounding his work with patients to cure their cancer. He also highlighted the personal challenge of his mom’s diagnosis with breast cancer.

Iyengar also specializes in exercise oncology, which he highlighted as an emerging field in breast cancer. He has worked on numerous trials seeing how diet and exercise can impact the outcomes of one’s cancer treatment.

The conversation also focused on work/life balance and how he has almost found the key to juggling both. His biggest advice is to find work that excites and motivates you throughout your day-to-day.

What made you interested in studying medicine, specifically breast oncology?

I’ve always been interested in physiology and the science behind medicine. It was the interest in biology and physiology that drove me to pursue medicine as a career. It was also the realization that I enjoy working with people. The perfect application of the science of biology and physiology was medicine for me because it brought together that interaction with people, as well as getting to do research and investigate novel pathways, novel medications, interventions, and so forth. Medicine is the perfect intersection of interaction, plus science.

Oncology specifically took me a while to get there, but I eventually became interested in it because as I went through my medical school training and my residency training, it became clear to me that, that interaction with people was central to my love and passion for medicine. That interaction with people is sacred in oncology, because you develop longitudinal relationships with people, particularly at some of their most vulnerable times. It's a real privilege to be able to have that trust to be able to walk into an exam room and enter that sacred place of trust and relationship with a person. That’s what drove me to oncology: that profound relationship.

In addition, there’s so much going on, research-wise in oncology, and it's one of the few disciplines where there are just so many biologic pathways involved in terms of tumor signaling tumor-host signaling, microenvironment, immunology, metabolism, that it’s an area where no matter what your scientific interest is, you’re likely to find a home or a place for your passion, scientifically, in oncology. Sticking with that theme of the blend between human interaction and science, which initially brought me to medicine, oncology was an even deeper dive into those 2 passions.

One of your main focuses is exercise oncology. How would you define this, and why is it an important field to study?

The field of exercise oncology is relatively new. Certainly, the field has been around for some time and largely focused on the recognition that exercise can help people feel better. There has been a large body of evidence that has now been established that exercise, particularly aerobic exercise, is helpful in terms of improving fatigue, as well as several other patient-reported outcomes, mental health benefits, and so forth. During cancer therapy, I particularly became interested because there has been some preliminary, preclinical data mostly, that exercise may also have some direct antitumor effects, or it may synergize with cancer therapies to improve response to those therapies. It may help to prevent resistance developing to several of our cancer therapies.

We’re embarking on several clinical trials, to translate some of the preclinical findings that support those hypotheses to humans and to determine if exercise indeed, can be helpful in terms of cancer-specific end points. The observational data suggest that exercise can be helpful in terms of reducing the risk of developing several cancers, at least 26 cancers, and exercise can be helpful in terms of outcomes like survival outcomes after a cancer diagnosis. We have preclinical data; we have epidemiologic observations that exercise improves cancer-specific outcomes. Now, we’re just starting to see in prospective randomized trials, that those data may be validated. Indeed, we might be able to incorporate exercise as part of a cancer treatment plan. Certainly, if we have an intervention that helps people feel better, and it also improves their cancer outcomes, that would be a big home run.

The issue is most of the data that we do have is based on either observation, as I’ve been mentioning, or preclinical data. So much data are dependent on self-report or self-recollection, which is useful, but of course, can be mired with all kinds of errors and recall bias, and so forth.

It’s very important that we do test exercises in a precision way, the way that you would develop any new drug for developing cancer or for treating cancer. This is the paradigm that we’re using for studying exercise. We’re doing traditional dose-finding studies. The dose of exercise for 1 type of cancer may be different for another type of cancer. Or even within the same cancer, the dose of exercise for a metastatic cancer may be different than for an early-stage cancer. We need to do this phase 1, phase 2, phase 3 type of approach where we identify the appropriate dose of exercise, then take that dose forward into phase 2 testing and evaluate the preliminary efficacy. Finally, [we need to] validate [these findings] in larger phase 3 studies.

What is an accomplishment that you’re most proud of?

This is a hard question to answer. There’s a lot that I could say that I’m proud of. When I think about this question, I think of it as, what has brought me the most fulfillment? I could say 2 things to that. One is certainly patient care; it has been fulfilling and important to me—certainly challenging. That’s partly what makes it fulfilling. It’s not simply, “Oh, we got a great scan”, or “We were able to reduce the tumor volume.” As that’s all important, taking a whole-person approach to patient care, has been fulfilling.

I pride myself on the fact that when we’re treating a person’s cancer, we’re also treating that person. That is partly why I am interested in in lifestyle interventions like exercise oncology, because you can certainly hammer away at a tumor and give all kinds of chemotherapy or anti-cancer therapies. If that person is feeling miserable and has no quality of life and a short duration of response to that therapy, that's not necessarily the type of outcome that I would consider to be successful.

If you’re able to either control or cure cancer, while also improving a person’s quality of life and general well-being, that’s the outcome that I strive for. When I see that in my patients, and in the patients of my colleagues, that brings a lot of fulfillment. Pursuing that approach in my patient care has been something I'm very proud of secondarily, and this is sort of an extension of that.

Several years ago, we established the Healthy Living Program at Memorial Sloan Kettering [Cancer Center]. This is a clinical program that essentially strives to standardize everything that I’ve just said. We enroll patients who are diagnosed with cancer, essentially at the time of their cancer diagnosis. We systematically create a lifestyle care plan that complements their cancer therapy, and it could involve exercise, dietary changes, mental health interventions, ways to improve sleep, for example, cognitive behavioral therapy, and interventions that address financial toxicity. It's a whole-person, lifestyle plan that we tried to give in an individualized manner to people as they’re also gearing up to start cancer therapy.

People’s needs change during their cancer therapy, and in different stages of life. We try to keep that updated. I’m very privileged to work with a great team of clinicians and researchers that make up the Healthy Living Program, including nurse practitioners, nutritionists, exercise physiologists, mental health workers, and so forth. We’re looking at the data [which have] helped to improve the quality of life during cancer therapy. It’ll help improve overall outcomes, both in terms of cancer-specific outcomes and long-term risks, not just for cancer recurrence, but also for long-term complications of cancer therapy, like the development of diabetes, or cardiovascular disease. These types of lifestyle interventions are likely to reduce those long-term complications. I’m very proud that we have been able to establish a program like that here at Memorial Sloan Kettering. I hope we can continue to grow it and make it available to more and more patients.

Have you experienced any significant challenges throughout your career?

This field is riddled with challenges. That’s partly what makes it fun to try to get over them. Every day, we’re presented with challenges and patient care. Cancer is such an incredibly difficult and challenging disease to treat. From that aspect, that’s a daily challenge.

One of the biggest and most personal challenges that I faced was when my mom was diagnosed with breast cancer. On the one hand, when you’re in the field, it certainly is helpful, you can start formulating a plan right away and connect your loved one to the appropriate resources and people as quickly as you can. On the other hand, it's a double-edged sword, because your mind also goes to the worst possible places. After all, you’ve seen the worst possible things. This is partly what made it so challenging. I’m very fortunate to have a group of colleagues who are essentially like family, and they all came around us and helped us. I’m happy to say that my mom is now in survivorship and done with her cancer therapy and—knock on wood—doing well.

Have you found a good formula to help combat burnout and create a good work/life balance?

My view is this: you go into this field, especially a field like oncology, because you're passionate about it. The research that I do and the patient care that I do, while it is challenging, also brings fulfillment. That boundary between work and life is blurred, because if it’s a Sunday morning working on some of my research papers or protocols, I don't do that begrudgingly. I don’t sit there grumbling, saying “I wish I wasn’t working right now.” Part of that is because I’m excited to do that, and I can’t wait until Monday. Part of it is also because there’s so much to do that it has to be done during off hours.

The blurring of the work-life balance is what at least helps keep me sane, because what I try to do is the tasks that I’m excited about, and that motivate me. Those are tasks that I’m willing and able to do off hours. The tasks that may be more menial, and that I’m not so excited about, that’s the stuff that I tried to restrict to working hours.

At least if I am doing work on a weekend or late at night, I’m not feeling upset about it, because I’m doing something that I’m excited about. If I’m doing something I’m excited about, I’m not so upset about it. Having children and a family makes that a challenge. That balance is more difficult. I’m a big proponent of prioritizing family and you do what you have to do. There are certainly many Sunday mornings when I’m with my family and my kids and not doing work. Ultimately, at least for me, it comes down to most of us having to do work during off hours. If you’re able to do the type of work that you’re excited and passionate about, then it makes it not just bearable, but you’re excited to do it anyway, so it doesn’t feel like work.

Are you currently involved in any research that you’re excited to see the results of?

We have several trials in the exercise oncology space. We do have lifestyle trials which are testing, diet, and exercise interventions. We’ve just completed a diet and exercise intervention, where we tested a precision plant-based diet with caloric restriction plus exercise. This is during adjuvant hormone therapy. The goal of the intervention was weight loss. Hormone therapy, particularly in the adjuvant space for postmenopausal women is associated with weight gain. Weight gain is a major problem because people don’t like to gain weight, but there are also health problems associated with weight gain, including a higher risk of breast cancer recurrence.

The rationale for this study was to see if we can use this type of precision lifestyle intervention. I say precision because for each individual, we were able to calculate their weekly caloric needs, and modulate the exercise sessions as well as the diet portion to match those caloric needs so that they are steadily but safely losing weight, and importantly, monitoring their body composition.

As part of this trial, we sent Bluetooth-enabled scales to the homes of all the participants so they could measure their body composition. These were bioimpedance analyses and we could monitor their fat mass and their lean mass daily. If we started to see a drop in their lean mass, along with their weight loss, then we could modify the exercise prescription. Maybe to make it more intense, we could modify the nutrition prescription, maybe back off on the caloric restriction a little bit or add some protein, but do that in an individualized way. I’m happy to say that we've observed very significant weight loss and very significant improvements in body composition, fat mass loss and increases in lean mass. We’ll be presenting that data at the 2024 ASCO Annual Meeting.

Another big plus of that trial is the participants volunteered to do breast tissue biopsies before and after the intervention. We’ve also collected blood and stool. There are a lot of biological end points we’ll be able to look at. One of the big concerns is that aromatase inhibitors don’t work as well in the setting of obesity. One of the hypotheses is that there are higher levels of the enzyme aromatase in the breast tissue in the setting of obesity. We will directly measure if we can reduce aromatase expression with this type of intervention.

The other thing that I’m excited about is a trial like that is a very intensive high-resource trial. For that study, it’s largely a proof of principle, because we’re trying to show that when you induce those types of body composition changes and those types of weight changes, you can impact biological end points like aromatase expression. In the day-to-day clinical world, something like that may not be feasible unless we develop a program accessible to [patients]. One of our lines of research is looking at digital therapeutics, like apps that people can use in a more perhaps implementable way.

Most of the weight loss trials in breast cancer have relied on either in-person exercise, counseling sessions, or telephone-based counseling sessions. The telephone-based counseling sessions are certainly a lot more feasible than in-person in some of the precision trials that we run here. I’m excited to see the results of the BWel trial led by Linda Delahanty, MS, RDN, LDN, which is testing a telephone-based intervention for weight loss in the adjuvant setting for breast cancer. We have already seen preliminary data that they’ve reported showing it’s effective for weight loss. The primary end point of that trial is breast cancer-specific recurrence. We’re waiting for the data to mature and I look forward to seeing those results.

In the meantime, we just finished a smaller pilot study using a digital therapeutic app for weight loss with Noom in women who have breast cancer. We found that that was a very accessible, convenient, and effective way of inducing weight loss after a breast cancer diagnoses. We anticipate that paper to be coming out shortly; it was just accepted for publication and should be out soon.

Reference

Delahanty LM, Wadden TA, Goodwin PJ, et al. The breast cancer weight loss trial (Alliance A011401): a description and evidence for the lifestyle intervention. Obesity (Silver Spring). 2022;30(1):28-38. doi:10.1002/oby.23287