A Field in Motion: Fighting Cancer with Exercise

(From left) Lee Jones, Director of the Cardio-Oncology Research Program, with Research Study Assistant Bharvi Patel, Exercise Physiology Manager John Sasso, and Clinical Research Manager Kristen Aufiero.

(From left) Lee Jones, Director of the Cardio-Oncology Research Program, with Research Study Assistant Bharvi Patel, Exercise Physiology Manager John Sasso, and Clinical Research Manager Kristen Aufiero.

Using an approach that spans basic and clinical science, exercise scientist Lee Jones, Director of the Cardio-Oncology Research Program (CORP), and his team are designing and testing the effects of individually prescribed exercise training to prevent or minimize the adverse cardiovascular side effects of cancer therapy. They’re also working to answer this potentially paradigm-shifting question: Can exercise be an effective treatment for cancer itself? Here, Dr. Jones talks about some of this work.

Can you tell us a little about the relationship between exercise and disease?

If you look at the role of exercise in other noncancer chronic diseases such as heart disease or heart failure and type 2 diabetes, exercise is typically part of the standard of care. In fact, exercise is the central piece of treatment for a lot of these diseases. So for example, somebody who’s had a heart attack is referred to cardiac rehabilitation, in which exercise therapy is the primary component and everything else is built around it.

An exercise prescription is also one of the front-line therapies for the prevention of many diseases. If you go to your primary care physician and you’re at risk for one of the most common chronic diseases such as diabetes or cardiovascular disease, one of the first things he or she will talk to you about is lifestyle interventions, whether that’s stopping smoking, modifying your diet, or losing weight — and the conversation always, or should always, include participation in a regular exercise program. For cancer, there’s convincing evidence that regular exercise is associated with a significant reduction in the risk of certain types such as breast, colon, and prostate cancer.

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So what do we know — and not know — about the role of exercise in cancer?

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Watch Lee Jones and MSK dietitian Cara Anselmo in an upcoming webinar on exercise and nutrition.

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While we’ve recognized the critical importance of exercise therapy for the prevention and treatment of other diseases for decades, the value of exercise in people with cancer was left largely untouched until recently. The prevailing view was that cancer is associated with poor outcomes, and that patients who are either undergoing or have finished intensive cancer treatments would not be able to participate in or tolerate structured exercise training. Because of this, many patients were — and may still be — advised to rest and avoid strenuous exercise, particularly during treatment.

However, things are now changing radically for a number of reasons. Perhaps the most important is the enormous progress we’ve made in cancer screening and prevention as well as treatment. In combination, this now means that people are living longer than ever before with after a cancer diagnosis and that, accordingly, certain cancer diagnoses are no longer considered a death sentence. Today, with nearly 14 million people in the United States living with a history of cancer, exercise has gained a lot of traction as part of the survivorship movement.

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Can you talk in a general sense about the type of work you and your research team are engaged in?

In the CORP, we are essentially focused on two fundamental things. The first is, are there better ways to lessen the immediate and long-term cardiovascular side effects of cancer treatment? Paradoxically, improvements in therapy for cancer have given people sufficient life spans to put them at risk for suffering the [late] effects of therapy, sometimes years after that therapy is over.

As part of their treatment, patients can receive a cocktail of different therapies — surgery, radiation, chemotherapy. We’re finding that these treatments, while effective at controlling the growth and progression of cancer cells, also cause damage to the components of the cardiovascular system, especially the heart, as well as the skeletal muscle. Together, this leads to a dramatic decrease in patients’ ability to exercise and even perform normal activities of daily living.

What we’ve learned is that cancer therapy leads to a dramatic reduction in a patient’s cardiovascular reserve capacity — commonly known as your fitness level  — and it appears to stay impaired even years after therapy. In fact, we’ve found that even a short course of chemotherapy has the same impact on the cardiovascular system as ten years of normal aging. That’s not good at all! But the good news is that in our clinical trials, we’re discovering that these effects can be attenuated in individuals who participate in structured exercise training prescriptions.

Our second major focus is understanding and harnessing the potent therapeutic properties of exercise as a form of cancer treatment to prevent recurrence and even help conventional or novel cancer drug therapies work more effectively. We want to discover if and how exercise impacts tumor biology, both in the early and advanced stages of disease.

We’re actually trying to approach the development and investigation of exercise treatment as you’d think about the development of a new drug. The drug we’re testing just happens to be called exercise, but I believe that the way we test it should be no different. In our program, we are trying to adopt, whenever possible, the same type of sequential study steps with similar types of endpoints that oncologists and cancer biologists use in the development of new targeted therapies — we think of it as precision exercise treatment.

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Is there a project that stands out as an example of this approach?

Here’s a good example: We’re interested in the testing the efficacy of exercise across the entire cancer trajectory, from prevention to advanced disease. To this end, we’re about to launch a study looking at the earliest stages of cancer development.  When we see patients in the clinic — after they’ve been diagnosed — a lot of the very early events in the development of the disease have already occurred. I want to look at how exercise might be affecting some of these. 

To do this, we’re going to perform a randomized controlled trial in women diagnosed with atypia [abnormal changes within the breast tissue]. These changes put them at significantly higher risk of developing invasive breast cancer. A total of 100 women will be assigned to a low, medium, or high dose of six months of supervised aerobic training [treadmill walking] — low being 75 minutes a week, medium being 150, high being 300 minutes. The fourth arm, the control group, will be women who will receive the usual standard of care [with no additional prescription for exercise]. All our aerobic training sessions are individualized to participants based on their fitness levels, which we measure at the beginning of the program using a sophisticated exercise stress test.

Before randomization, all women will undergo a battery of assessments including a core biopsy of the normal breast tissue. After six months, the biopsy will be repeated and we’ll be able to evaluate, for the first time, whether aerobic training lowers the expression of genes in the normal breast tissue that are known to promote breast cancer, and the optimal dose of exercise to stimulate these changes. What’s also unique about this study is that we’ll be performing a study in mice that is the mirror image of the human clinical trial, known as a co-clinical trial. Using this approach, we’ll be able to learn things in the mouse study that will inform analyses in the human trial. To my knowledge, this is the first study ever to adopt this approach in clinical exercise science in any chronic condition. 

Similarly, we’re going to be starting a randomized clinical trial in men with early-stage prostate cancer who are part of MSK’s active surveillance program. In this approach, treatments such as surgery or radiation therapy are deferred because tests show that the tumor is currently not life threatening or is at low risk of progressing. Our trial is going to test the effect of 24 weeks of supervised aerobic exercise versus the usual care on the prostate microenvironment [the cellular environment in which a tumor exists] and cancer-related anxiety among these men. Again, to my knowledge, this will be the first trial to study the effects of exercise on changes in the tumor itself.

Findings from both these studies will provide unique insights into the effects of exercise on tumor and tissue biology as well as the biologic mechanisms underpinning these effects. This will help us design future studies as well as optimize the efficacy of exercise.

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You’re also interested in cancer recurrence and metastatic disease and the potential impact of exercise in these circumstances.

I am. I’m very interested in prevention of recurrence and even the role of exercise in individuals with advanced disease. We’re starting to explore if and how exercise might affect the course of disease in these populations.

In terms of metastasis, I think exercise not only changes things like the breast tissue but also alters the microenvironments in tissues such as the lung and bone marrow — those places in the body where metastatic cancer cells may be dormant. I believe exercise may be able to actually change the microenvironment of such tissues to keep metastatic cancer cells asleep for longer — and perhaps even permanently. This is an area we’re studying collaboratively with various colleagues at MSK.

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Your work spans both laboratory and clinical research.

It does. Along with clinical studies in patients, we’re also starting to build a robust laboratory research program. Among the things we’re doing is working with mouse models as well as zebrafish [in collaboration with physician-scientist Richard White’s laboratory in the Sloan Kettering Institute] to study what’s going on at the molecular level to better elucidate the effects and underlying mechanisms of exercise training on cancer initiation and progression.

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You joined MSK in February 2014 and so are relatively new to the institution. Can you tell us how you feel about your experience so far?

My expectations have already been far exceeded. Across the board — from oncologists to the clinical trials office and various administrative bodies — the support has been nothing short of incredible. I came to MSK because our program goal is to make precision exercise treatment part of the standard of care for people with or at risk of cancer. To accomplish this, we need to do the best science and build a convincing evidence base, and that requires that we be at the best cancer center. MSK is that place! 

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Would it be possible for me to participate in this exercise trials? I'm a breast cancer survivor. I just had a mastectomy on May 4th. At MSKCC in Manhattan. My oncologist made a lot of emphasis on exercise. I would more than glad to participate in the study.

Karla, thank you for your interest in the trial. You can call Dr. Jones’s office at 646-888-8102 to discuss the trials they’re about to open and your potential eligibility.

I do water aerobics 150 minutes a
Week &iWork w/a trainer an additional hour does that work

We are sending you a private message about this to the email that you provided.

My sister has just diagnosed with pancreatic cancer. She wanted a second opinion before surgery. Her doctors say they need to do the surgery immediately. How can she get in touch with your team.

Exercise is key for me. Stage 3 b rectal cancer NED 3 years.
My mantras are Just keep moving and Sweat a LIttle EVERY DAY.
The physical and emotional benefits are amazing.
If there is a trial and you want to use me, lets chat. I am getting back into cycling (as my body function permits) and strength training to keep my bones strong now that I am in menopause (thanks cancer). I do yoga as well for pelvic floor strength. I am a volunteer with a Livestrong program at my YMCA and have spoken twice on their behalf. Anything I can do to give back to my hospital and team at MSKCC would thrill me to no end. PS 14 laps around the 15th floor at main campus = 1 mile.

I have stage 2A lung cancer. I trudged on the elliptical machine for a minimum of 30 minutes every day during my chemo other then the day of chemo administration. My chemo drugs were Cisplatin and Alimta, my side effects from the drugs were minimal. When I was done with chemo i was back in the pool for a mile a day. I think excerise is keeping the beast at bay.

Anerobic exercise and cancer. Lactic acid increase and lack of oxygen. Fred Lebow probably was running anerobicly, could this grow cancer cells.

Thank you for your comment. We passed your question on to Dr. Jones, and he responds:

Very interesting question. The intensity of exercise is often classified as aerobic vs. anaerobic but the truth is that exercise is never really one or the other - when you exercise there are contributions from both systems. It is true however that as exercise intensity increases the contribution from the anaerobic system starts to increase especially when exercise intensity goes beyond 70% of someone’s maximum capacity. At this point, the muscle cells can longer use oxygen to create energy but have to rely on other systems which can produce energy very rapidly but do not last as long and create a lot of waste products as a result. The waste products is in the form of lactic acid. This occurs in the muscle cells, not all cells of the body, and likely not cancer cells since cancer cells already predominantly use anaerobic metabolism even when there is sufficient oxygen being delivered (this is called the Warburg effect). The lactic acid that is released from exercising muscle cells is very rapidly removed from the body so I do not think it would impact lactate levels in cancer cells. In fact, we have shown in preclinical research that exercise actually increases oxygen levels in tumors and decreases hypoxia - which we believe may contribute to anti-cancer effects of exercise. I hope this answers your question.

I was diagnosed with uterine cancer 8 years ago. Chemotherapy followed surgery - I walked every day, did weight machines and treadmill at the Y and swam twice a week. This was at a low level. Now I continue to exercise daily at a moderate level. Feeling great - not too bad for 77 year old gal.

Jan, we’re glad to hear you’re doing well!

I am a 17 year cancer survivor. I was treated at MSKCC. All during treatments I walked 3 miles a day either outside or inside on a treadmill if the weather was not ideal. Today, I continue to walk, run (half and full marathons), cycle and lift weights. I've never felt better!

Two doctors (one at MSK, one outside) have told me to LIMIT my exercise since it can impair the immune system and create inflammation, which provides the environment for the growth of cancer. I'm 49 and was treated for endometriosis related adenocarcinoma with surgery, radiation and chemo, which I completed five months ago. I'm a two time Ironman and a lifelong competitive athlete whose exercise routine can include training for marathons and 50-75 mike bike rides. I'm also considering training for another Ironman in a few years; training for that peaks at 15-20 hours of relatively low heart rate exercise per week. Obviously, my health is my only concern and I don't want to jeopardize it in any way, but I also love endurance training. I'd really appreciate your group's thoughts.

Hello and many thanks for the excellent question. Let me see if I can break this down a little.

Acute, single bouts of exercise, particularly those that are high-intensity, are associated with an increase in levels of inflammation as well as free radicals in the muscle tissue — it’s almost like a damage response. In this sense, it could be interpreted that exercise is “bad.” However, on the basis of current evidence, we know that this initial damage response to exercise is actually beneficial and physiologic in nature. Indeed, the increases in free radicals and inflammatory markers are critical to stimulating the release of other numerous protective factors such as anti-inflammatory proteins as well as anti-oxidant/defense pathways that essentially “up regulate” the body’s ability to tolerate higher levels of exercise stress. In other words, this is a critical part of the body’s innate ability to adapt, and for performance to increase in response to exercise.

So, as you do more exercise training sessions (i.e., chronic exercise training), all your body’s systems — including of course the cardiovascular system — become fitter. Essentially, you have greater capacity to deliver and utilize oxygen during exercise. In concert with these changes, many biological aspects also improve including your metabolism and immune function. It was always thought that this was a linear relationship, i.e., the more exercise you do the better the response.

However, it’s not clear that this is true. There may be a critical threshold of exercise volume/dose that if you go beyond this, more exercise could actually be detrimental. It’s what we call a U-shaped relationship. We do not know what this point is, but it is likely highly variable among individuals. For most individuals this point is not relevant since they do nowhere near enough exercise to reach this threshold. However, it is commonly seen in athletes who become overtrained. You have probably seen this: It doesn’t matter how much training they do, they always underperform and feel tired, and may be constantly injured. This is a classic model of overtraining — doing too much without sufficient rest or sequencing of exercise sessions.

Now as I mentioned, the upper threshold of overtraining relates to a very high volume of exercise in the general population but we do not know if this level is different in persons who are recovering from cancer or undergoing cancer treatment. We do know that the body’s ability to exercise is dramatically impacted by cancer and cancer therapy so it’s conceivable that this upper threshold is similarly reduced.

In our studies at MSK, we have found initial evidence that exercise training is associated with improvements in immune parameters as well as lower inflammation but this was in response to exercise training for around 150 minutes per week at a low to moderate intensity (although we also applied some high-intensity as well0. These individuals were closely monitored and the exercise sessions were carefully tailored to each participant.

Quite honestly, we don’t know how the body responds to high levels of exercise such as those conferred by events like the Ironman in persons with cancer — no one has studied it. However, there is no argument that such events are associated with considerable stress on the body’s system that can last a long period of time. It is important to remember that exercise is like a drug: it confers lots of different effects on the body that are mainly beneficial but it needs to be performed and dosed appropriately. Rest and recover sessions (and adequate supporting nutrition and sleep) are absolutely critical.

I would like to be part of clinical trials. I have spoken to you before. Thanks for your time,
Nicole Stromer

Nicole, thank you for your interest in clinical trials. You can call Dr. Jones’s office at 646-888-8102 to discuss the trials they’re about to open and your potential eligibility.

I was diagnosed with Stage 4 CC late 2014 (37 years old, no family history) and had surgery to remove the tumor from my colon and a small spot on the liver. Starteded chemo (Folfox) in Feb 2015 and walked 3-5km daily during my chemo week and jogged or rode my bike in the "off chemo" weeks. I was living life like a yo-yo but I believe the exercise helped me tolerate the chemo better and now that it's approximately 1 month after my last round of chemo I have increased my daily running to 4kms per day and have returned to the gym to include some weight training into my exercise. I feel fitter then ever with no limitations or side effects due to surgery and chemo and I believe exercise had a big role to play in my recovery.

Dear TD, we are glad to know you are able to keep active and that it’s helped you during your recovery. Thanks for sharing your experience.

I was diagnosed with stage 4 lung cancer and given months to live in 2009. There is no question in my mind that active exercise has bought me several years, even with a recurrence in 2014. Interesting side event. I was on a pembro trial and it almost killed me- Luis-like. I think that shows my immune system was strong and did not need an excelerant

Hello... I was wondering if you are still accepting people in the exercise trial or if there are any new exercise trials starting. I was diagnosed with Metastatic Breast Cancer to the liver in Jan. 2016. Thank you, LIsa Kutra

Dear Lisa, we are sorry to hear about your diagnosis. We have several clinical trials involving exercise that are currently open, one of which specifically involves people with metastatic breast cancer: https://www.mskcc.org/cancer-care/clinical-trials/14-170. If you are interested in learning more about this trial or making an appointment, please call our Physician Referral Service at 800-225-2225. Thank you for reaching out to us.

I have PMP cancer. I am currently on Capecitabine and Avastin (14/7 cycle). Lots of fatigue. I am planning on going to the 7/7 cycle. I have always be very active (Marathons, Triathlons, etc). Can you tell me the optimal exercise regiment? I am hoping a 7/7 cycle will better allow me to get back on an exercise regiment. Also should I investigate the trail?

Dear Tim, we are not able to make specific recommendations on our blog, and would encourage you to follow up with your oncologist to discuss the most appropriate form, frequency, and intensity of exercise for your particular circumstances. If you are interested in learning more about the exercise trials we currently have open, please visit https://www.mskcc.org/cancer-care/clinical-trials/search?keys=exercise&….
Thank you for reaching out to us.

I have Had cancer for the last 7 years of my life had chemo and radiation interested in exercise program study.

Dear Dorothy, we are sorry to hear about your cancer diagnosis.

To learn more about our clinical trials involving exercise, please visit https://www.mskcc.org/cancer-care/clinical-trials/search?keys=exercise&…

If you have any questions regarding these studies or would like to make an appointment for a consultation, please call our Physician Referral Service at 800-225-2225. Thank you for reaching out to us.

I had chemo, R lower lobe removal, and radiation + chemo for lung cancer in 2008. It came back to lymph node just above my right collar bone in 2012, removed with more chemo (far less aggressive) and radiation. I think I'm fine right now - am working, walking my dogs and feel great w/small exception that sometimes walking fast I can easily get out of breath. Is there a guided exercise program/trial that I could participate in? I am 67 years old and healthy in every way except for a bad back. I used to take a lot of dance but can no longer because of most of my back having been fused. I know I need exercise though, and that was before learning it can help with further mets.

Hi, Marianne, we’re sorry to hear about your diagnosis but it’s good to know that you’re feeling well and have a good quality of life. It’s best to talk with your physician before starting up any exercise program. Only he or she can advise you on the specific type, frequency, and intensity of exercise that’s is best for your particular circumstances. Thank you for reaching out to us.

I've just graduated with a degree in Exercise Physiology and am pursuing a doctorate in the same field. I am very interested in working with Dr Jones and assisting him with any of his research this summer.

Would this be possible?

How do you get a specific exercise routine for your particular type of cancer?

Hi Bill, thanks for your question. We recommend you ask your oncologist for a referral to a physical therapist who specializes in working with cancer patients. If you are in the NYC area, you may want to reach out to Integrative Medicine Center, which offers a number of classes for people who have had cancer. You can learn more at https://www.mskcc.org/cancer-care/treatments/symptom-management/integra….

Is there a web page where I can always go to see all the publications of your research results? I want to stay up to date on what you are discovering.

I am interested in any work you might be doing and/or any comment you might have about ketogenic diet and/or metformin to suppress tumor growth especially in prostate cancer

Dear Don,
We forwarded your question about metformin to MSK medical oncologist Michael Morris who specializes in treating men with prostate cancer. This was his response: “The use of metformin to either treat or prevent prostate cancer has long been a topic of interest for investigators and patients alike. There has been both preclinical work and retrospective analyses of patients that have suggested that drugs like metformin may favorably modulate prostate cancer growth; these data are now being explored in prospective studies as well. At present, I would regard metformin as exploratory in prostate cancer, but this story is an evolving one, and one which all of us follow with keen interest, especially as it is readily available, well tolerated, and commonly used for the treatment of diabetes.”

As for ketogenic diets, our experts maintain that there is not currently enough information to recommend ketogenic diets (or any other specific diet) as a way to treat cancer.

Thank you for your comment.

I would love to take part in an exercise trial. I am stage IV nsclc Diagnosed Oct 2015. I do keep active and try to exercise regularly. I feel great!

Dear Debbie, we’re glad to hear you’re feeling good. If you are an MSK patient, you can discuss participating in a trial here with your doctor. If you’re not at MSK, you could ask your doctor if there are any trials available where you’re being treated. Thank you for your comment, and best wishes to you.

What a wonderful thing to investigate. I am a Hodgkin's and Breast Cancer survivor. All my treatments have been at MSKCC. I now have CHF due to my treatment and am being followed by Dr. Steingart. (Thank you Dr. Steingart). I hope that others can avoid this long term effect. When you have a program for long term survivors, sign me up.

Dear Teresa, thank you for your comment. If you’re interested in participating in any trials, you can discuss this with your MSK team.

Just learning about this via some podcasts I am listening. I was diagnosed with Thyroid Cancer with bone metastasis. I am (used to be) a competitive track athlete when they discovered this in 2013. It was in my arm and spine. But once they took away the pain, I was back to normal but now the side effects of RAD and RAI might be creeping up and I am looking for some exercise program or trials for someone like me. Recently I have developed metastasis in my pelvic bones. Although I am not overweight and have decent health, not being able to exercise as I used to, is making a bit not normal "me". Any help in this matter would be greatly appreciated.
Any guidance to coaching, trials etc.

Dear Indu, we’re sorry to hear you’re going through this. You may want to consult with a physical therapist who has experience in working with cancer patients. If you are in the New York City area, you may want to check out the offerings at our Integrative Medicine Center. You can learn more at https://www.mskcc.org/cancer-care/diagnosis-treatment/symptom-managemen… Thank you for your comment, and best wishes to you.

I am 10+ years post successful treatment of a stage III breast CA with chemo surgery chemo radiation. I am a physical therapist and had felt that during chemo I would benefit from cardio exercise the day after my infusion. I had this image of wanting my chemo to be systemically widespread! Has anyone ever looked at whether cardio exercise increases/aids the effectiveness of chemo? Thank you Eileen Collins

Dear Eileen, some studies have suggested that exercise may improve the effectiveness of chemotherapy, but more research is needed. We recommend that cancer patients speak with their doctors about participating in an exercise program during cancer treatment. Thank you for your comment, and best wishes to you.

It's been two years since this article was published, and I searched PubMed but I could not find any papers associated with this trial. Has results of this study been published?

Is it possible that you will expand your study to men undergoing ADT treatment. If so, would you allow someone in another clinical trial to participate? Could participation be outside the main campus, say West Harrison? Bob Rohr

Dear Bob,

Thanks so much for your interest in our research program here at MSK studying the role of exercise following a diagnosis of cancer. Thanks for your question. Unfortunately, at this time do not have plans to open a study investigating the role of exercise in men receiving ADT for prostate cancer. One of the reasons for this is that there has already been quite a lot of work on this very question. It is established that ADT may be associated with a variety of negative side-effects including weight gain, muscle loss, and fatigue - however, over 8 relatively large and well-conducted studies have demonstrated that exercise, specifically the combination of weight training and aerobic (cardio) training approximately 3 days a week can significantly attenuate these side-effects. As such, I recommend chatting with your oncologist about your suitability to start an exercise program, and as appropriate, I’d be happy to provide some recommendations on the types and intensity of exercise that may be of benefit.

Best, Dr. Lee Jones

Hello, I was diagnosed with Stage 2 Ovarian Cancer. 30 biopsies taken and no evidence of cancer. I am doing 6 preventative chemo treatments to keep the beast at bay. I have completed 3 of 6. Are there exercise trials that are available? I went to the gym everyday and after surgery walked 3-4 miles per day. The chemo has slightly slowed me down (issues with constipation which I never had), and need to get back to my routine. Please let me know and thanks. Oh and I do participate in the MSK Interactive Program with massage and reflexology!