A Field in Motion: Fighting Cancer with Exercise

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(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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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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Comments

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My mother has metastatic ovarian cancer and came to MSK for second opinion about treatment. Exercise was never mentioned. Is this only beneficial for breast and prostate patients or can you recommend anything I can share with her? Thank you

To whom it may concern, my husband is a patient at MSK and is currently seeking treatment for Stage IV Metastic Colon Cancer (BRAF mutation).

Whilst he is being responsive to treatment, I do wonder if there are any trials he can participate in.

Up until treatment, my Husband was an active man who went to the gym daily. A former Rugby player, he was always running, attended CrossFit classes, did weight training and boxing.

Even if there is no trial, we would at least like to speak to Dr.Jones to recommend some new routines as we find a new normal for him to include daily exercise back into his life. Thank you kindly.

Dear Rima, we’re sorry to hear about your husband’s diagnosis. We recommend that you discuss this with his current healthcare team at MSK. Thank you for your comment and best wishes to both of you.

I am a MSK patient (age 59): 2014 BC (lobular, stage 3, ER+), then 2018 mets to ovaries. After surgery to remove ovaries I had a pulmonary embolism. In addition to new BC meds (Faslodex & Ibrance), I'm now on Xarelto (for life!). My doc says I should walk. Before discovery of mets I was (am!) a triathlete so just walking is not going to cut it. But now I wonder about how being on blood thinner will affect training. It's been 6 months and I am hesitant to push myself. Can you weigh in on the effect of blood thinners on exercise, esp given that exercise creates micro-tears in muscle? Thx, LG (PS I'm also dealing with fibromyalgia & post herpetic neuralgia but I think ramping up exercise will help those - any thoughts on that?)

Dear Linda, we recommend that you discuss this with your MSK care team. Thank you for your comment and best wishes to you.