Sloan Kettering’s Quest to Prove Exercise Can Inhibit Cancer

Dr. Lee Jones and his team at Memorial Sloan Kettering Cancer Center in New York are studying whether an exercise regimen can inhibit the spread of cancer and help prevent its recurrence. From left, Dr. Jones, Marsha Patel, John Sasso and Kristen Aufiero. Photo: Memorial Sloan Kettering Cancer Center

By Lucette Lagnado

Feb. 29, 2016 12:38 p.m. ET

Researchers are testing an intriguing new weapon for patients battling cancer: rigorous physical exercise.

Studies and clinical trials at Memorial Sloan Kettering Cancer Center in New York City aim to find out if a regimen of exercise training can inhibit or delay the spread of a malignant tumor and help prevent its recurrence. An early-stage trial currently under way involves 72 women with stage 4 breast cancer, which has spread to other parts of the body and is generally considered incurable.

Scientists say the research, part of an emerging field known as exercise oncology, could take years to prove a link between exercise and cancer. If successful, they hope exercise someday will become a standard of care in cancer treatment, along with conventional therapies such as surgery, radiation and chemotherapy.

ENLARGE

Kristen Bouderau, who has stage 4 breast cancer, is supervised by an exercise physiologist as she walks on a treadmill at various intensities and duration for 30 to 60 minutes, three times a week for 12 weeks as part of a trial at Memorial Sloan Kettering.Photo: Caitlin Hool for Memorial Sloan Kettering Cancer Center

Previous studies have found, for example, that breast-cancer patients who exercise have a lower risk of recurrence and are less likely to die from their disease than women who are inactive. But the findings, from observational studies, aren’t definitive, experts say. Exercise also has been shown to help some cancer patients tolerate the debilitating effects of chemo and radiation treatments.

The new research at Sloan Kettering includes randomized, controlled studies—considered the gold standard for scientific inquiry—seeking to prove that exercise can alter the biology of a tumor, thereby inhibiting or slowing its growth, says Lee Jones, who is leading the Sloan Kettering effort.

Dr. Jones, an exercise scientist with Sloan Kettering’s Cardiology Service, whose research has focused on oncology, says studies with animals suggest the idea of reversing tumor growth with exercise may be possible. A study he co-authored, published last year in the Journal of the National Cancer Institute, found that “exercise statistically significantly reduced tumor growth” in mice with breast cancer.

Some doctors caution that some cancer patients can’t tolerate even moderate exercise. Chemo drugs can take a heavy toll on the body, for example, and cancers that metastasize to the bones could raise the risk of fractures, says Anne McTiernan,a doctor and researcher at the Fred Hutchinson Cancer Center in Seattle.

Still, Dr. McTiernan says previous research has made her optimistic that physical activity can affect tumor behavior and may lower cancer recurrence, though more research needs to be done.

There is “no question” that exercise is important to overall health, but data showing it can combat or prevent cancer is “poorly supported,” says Daniel Hayes, an oncologist and professor of breast-cancer research at the University of Michigan Comprehensive Cancer Center in Ann Arbor. Dr. Hayes, who is the incoming president of the American Society of Clinical Oncology, says he supports further research, but emphasizes “the importance of not abandoning standard treatments in hopes that diet and exercise will replace them.”

In the trial of stage 4 breast-cancer patients, a total of 72 women, who are also receiving standard cancer treatments, have been randomly assigned to either 12 weeks of rigorous, structured exercise, or to a gentler program of stretching. Fifty women have so far completed the trial. The early-stage study is meant to determine if the women are safely able to tolerate the workout, done on a treadmill. Results are expected later this year, Dr. Jones says. 

Patients are initially tested to establish their baseline capacity, which helps determine the duration and intensity of their workouts. Members of the research team monitor the patients’ vital signs during the workout and stretching sessions.

Dr. Jones says he hopes to move on to a phase 2 randomized trial to test whether women who do intense exercise show improvement. Signs could include a tumor remaining stable for a longer time, better overall patient survival or improved quality of life. Conclusive evidence on whether exercise can inhibit cancer’s progression could take as long as 15 years to gather, he says.

Leslie Plush completed Sloan Kettering’s phase I trial of exercise and cancer last year. Ms. Plush, who got married a few months ago, says she found herself on New Year’s Eve wishing that ‘my life was going to be good and I was going to be healthy.’ Photo: Leslie Plush

Patients with stage 4, metastatic breast cancer have an average life expectancy of about three years from the time of diagnosis, although some women live much longer. 

Kristen Bouderau, a costume designer in New York City, was diagnosed in 2012 with metastatic breast cancer that spread to her spine. The 50-year-old gets weekly chemo treatments. She also works out at a Sloan Kettering rehab facility three times a week as part of Dr. Jones’s exercise trial. An exercise physiologist stands at her side monitoring her pulse and breathing and takes her blood pressure every five minutes to make sure she is tolerating the exercise. 

After 11 minutes on the treadmill, Ms. Bouderau is chipper but a bit out of breath. “I haven’t burned off half a bagel yet,” she jokes. She is hopeful the workout will help her. “I want to be here for my 12-year-old [daughter]. I would like to be here when she is 18.” 

Dr. Jones says his team carefully tells participants the study isn’t designed to help with their cancer, that it isn’t known if it will.

It isn’t clear how exercise might work in the body to affect a tumor. One theory is that physical activity can reduce levels of insulin and other factors that have been linked to greater cancer risk. Exercise also can boost the immune system, and it might affect the environment in which the cancer is growing. “Cancer doesn’t grow in a vacuum, and what is around the tumor can either support its growth or can inhibit it,” says Jennifer Ligibel, an oncologist at Dana-Farber Cancer Institute.

“Twenty years ago when I was in training we thought that people with cancer, we needed to give them more rest. [Now] we realize that physical activity can be part of the treatment,” says Ernest Hawk, vice president of cancer prevention at MD Anderson Cancer Center in Houston, who helps lead prevention efforts at the American Association for Cancer Research.

Karen Cadoo, an oncologist at Sloan Kettering who specializes in ovarian cancer, is working with Dr. Jones on another experiment to see if a regimen of exercise can help a group of her patients cope with the side effects of chemotherapy. Typically, 50% of women with ovarian cancer who are prescribed intense chemotherapy aren’t able to finish the treatment because of such side effects as persistent nausea or extreme fatigue, she says. Since patients who tolerate more rounds of the strong chemo have better outcomes, exercise could perhaps help improve their survival, Dr. Cadoo says.

Animal studies Dr. Jones is running in basement laboratories at Sloan Kettering also are investigating whether physical activity can delay or prevent the spread of cancer. In one experiment, groups of zebrafish swim three hours a day against different strength currents in special tanks known as swim tunnels. The zebrafish have metastatic melanoma, and because they are translucent, the cancer shows up as a little black blemish. 

In another experiment, groups of mice at risk for breast cancer are racing on treadmills to test whether exercise, and how much, will keep them from developing a malignancy or delay its onset. 

Leslie Plush, 50, has been getting various treatments for her stage 4 metastatic breast cancer. She also completed Dr. Jones’s phase I trial last year. Ms. Plush, a decorative artist in New York City, says she continues to exercise at home and finds she can walk faster and is less out of breath.

Ms. Plush, who got married a few months ago, says she found herself on New Year’s Eve wishing that “my life was going to be good and I was going to be healthy.” She hopes the exercise regimen and other treatments will help stave off her cancer. Her new husband “has been there for me through it all,” she says. Now she would like to be there for him “as much as possible and for as long as possible.” 

Write to Lucette Lagnado at lucette.lagnado@wsj.com

The secret to staying young? Get on your bike!

Want to stay younger for longer? It could be as easy as riding a bike.

For cycling really does keep the body – and the mind – young, scientists say.

A study of fit amateur cyclists aged 55 to 79 found many were physically much younger than most people their age.

A study of fit amateur cyclists aged 55 to 79 found many were physically much younger than most people their age

The 81 male and 41 female participants underwent extensive tests, including of their hearts, lungs, reflexes, muscle and bone strength and mental ability.

Despite an age range of 25 years, older members of the group had similar muscle strength, lung power and exercise capacity to the younger participants.

In a simple test to show a person's risk of falling over – which measured how long it took participants to stand from a chair, walk three metres, walk back and sit down – even those in their seventies achieved times expected of healthy young adults, the Journal of Physiology reports.

The participants were all able to cycle long distances, but you do not need to be super-fit to enjoy the benefits of activities like cycling – as it is staying active at any level that is important.

Dr Ross Pollock, who led the team of scientists from King's College London, warned that most of us are inactive, which causes 'physiological problems at any age'.

The 81 male and 41 female participants underwent extensive tests, including of their hearts, lungs, reflexes, muscle and bone strength and mental ability

Professor Norman Lazarus said that staying active can 'buy you extra years of function', adding: 'Cycling not only keeps you mentally alert, but requires the vigorous use of many of the body's key systems, such as your muscles, heart and lungs, which you need for maintaining health.'

The cyclists were recruited deliberately to exclude effects from a sedentary lifestyle that may cause changes in the body capable of being confused with those due to ageing.

Men and women had to be able to cycle 100 kilometres in under 6.5 hours, and 60 kilometres in 5.5 hours, to be included in the study. Smokers, heavy drinkers, and people with high blood pressure or other health conditions were excluded.

Oxygen consumption rate showed the closest association with birth date, according to the results published in the Journal of Physiology. But even this marker could not provide an accurate indication of the age of any given individual.

Dr Pollock added: 'The main problem facing health research is that in modern societies the majority of the population is inactive.

'A sedentary lifestyle causes physiological problems at any age. Hence the confusion as to how much the decline in bodily functions is due to the natural ageing process and how much is due to the combined effects of ageing and inactivity.

'In many models of ageing lifespan is the primary measure, but in human beings this is arguably less important than the consequences of deterioration in health.

'Healthy life expectancy - our healthspan - is not keeping pace with the average lifespan, and the years we spend with poor health and disabilities in old age are growing.'

Co-author Professor Stephen Harridge, director of the Centre of Human & Aerospace Physiological Sciences at King's College, added: 'Because most of the population is largely sedentary, the tendency is to assume that inactivity is the inevitable condition for humans.

'However, given that our genetic inheritance stems from a period when high levels of physical activity were the likely norm, being physically active should be considered to play an essential role in maintaining health and well-being throughout life.'

Cycling Cadence: What is it & How to Improve Yours

If you’ve ever watched elite cyclists pedal, you’ve likely noticed how they glide along the road. Quickly, smoothly, efficiently. Their legs move in steady loops whether they’re going up a steep hill or riding on flat terrain. And a huge part of that ease is cadence.

Cadence is the rate at which a cyclist pedals. It’s the number of pedal revolutions per minute (RPMs). If you increase and train your cadence, you’ll improve your cycling efficiency, allowing you to pedal for longer, faster.

Why?

When you pedal faster, you put less strain (i.e. force) on your muscles with each stroke. You ride in a lower gear, and as a result, use your slow-twitch muscles. These muscles burn fat for fuel, are resistant to fatigue, and recover quickly when allowed to rest. Also, studies show a higher cadence means an increase in blood flow to the muscles – which in turn, means more oxygen in the blood and a higher aerobic performance.

On the other hand, a low cadence at a high gear is more taxing on the muscles. It uses fast-twitch muscles, which burn glycogen for fuel, fatigue quickly, and takes a long time to recover before they can be used again. In other words, muscle strength doesn’t last long, so you’ll start to feel the burn faster than at a higher cadence.

While you might think that pedaling faster would be harder on your cardiovascular system, but that isn’t the truth. The cardiovascular system is a highly efficient system. Unlike the muscular system, it doesn’t take long to recover, and it is only limited by its capacity – how much air it’s getting in at any given time – not by how much work has already been done.

So what’s the ideal cadence for a cyclist?

While there’s no one magic number, aiming for 90 RPM is a good goal to avoid leg fatigue and making the most out of those slow-twitch muscles. Average cyclists have a cadence of about 60 RPM; advanced and elite cyclists pedal anywhere from 80 to 100 RPMs.

All of that said, changing your cadence isn’t something you can do overnight – it takes months. Your body has adapted to your current cadence and changing it requires work from all of your body’s systems: neural, muscular, cardiovascular, metabolic, etc.

HOW TO DETERMINE + IMPROVE CADENCE

Regardless of whether you’re a recreational rider or a serious racer, practicing to ride at a higher cadence will make your pedal stroke more efficient. By maintaining a steady cadence throughout your ride, you’ll become a better rider. But remember, this doesn’t mean you need to pedal faster in the same gear. As you climb, adjust your gear, so it’s easier and keep your RPMs consistent.

Before you can increase your cadence, however, you need to determine where you currently stand.

There are multiple ways to determine your cadence. The most basic and straightforward – though not necessarily the most accurate – is to count the number of times your right knee comes up during a ride in 30 seconds and double it.

In general, to improve your cadence, start off with shorter extreme efforts as well as longer more modest efforts. Why? According to Bike Roar, “By hitting cadence numbers beyond the norm, you’re training your brain to fire signals in the patterns required for your muscles to contract far more rapidly. Then when you hit normal numbers, it doesn’t seem as hard.”

Really, Just One Drink? But what about exercise?

Just One Drink Raises the Risk of Breast Cancer, While Vigorous Exercise Mitigates the Damage.

Researchers found a link after analyzing 119 studies;
Sumathi Reddy WSJ May 29, 2017 7:00 a.m. ET

Borrowed from WSJ 5 29 2017


One glass of wine could increase your risk of breast cancer, according to a new study by the American Institute for Cancer Research and the World Cancer
By Sumathi Reddy

Bottom’s down: A new report finds that drinking even one glass of alcohol a day could increase the risk of developing breast cancer, while vigorous exercise mitigates the damage.
The type of alcohol doesn’t matter—wine, beer and hard liquor all pose the same risk.

The report, a joint effort of the American Institute for Cancer Research and the World Cancer Research Fund, was a review of 119 studies looking at how diet and physical activity impacts the risk of developing breast cancer in pre- and post-menopausal women. The studies included data on 12 million women and 260,000 breast cancer cases. The studies don’t show that alcohol causes breast cancer, but they do show an association or link.

A small glass of wine or beer a day—with about 10 grams of alcohol content—increases the risk of pre-menopausal women developing breast cancer by 5% and post-menopausal women by 9%, the authors concluded. A standard drink has 14 grams of alcohol.

“One thing that surprised me was that even at such a low level, drinking alcohol was statistically significant,” said Anne McTiernan, a cancer prevention researcher at Fred Hutchinson Cancer Research Center in Seattle, and lead author on the report.

Experts aren’t clear on why alcohol increases the risk of breast cancer. One theory is that alcohol increases the levels of estrogen in the blood, which is a risk factor for developing breast cancer. Also, alcohol can damage DNA, which is a pre-cursor to cancer.

Susan K. Boolbol, chief of breast surgery at Mount Sinai Beth Israel in Manhattan, noted that pooling many studies can lead to an imperfect analysis. The studies are retrospective so they involve asking women how much they drank, which isn’t always reliable data.

She said the important message is that all types of alcohol are equally harmful. “I have this discussion with patients all the time,” she said. “They say, ‘I only drink wine, or I only drink beer, and that doesn’t count.’ This was very, very specific that it does.”

Still, she said it’s unrealistic to recommend to patients that they completely abstain from alcohol. “We have to be reality-based,” she said. “Once we start saying “don’t do this, don’t do that,’ we lose patients. They stop listening. So I think it’s about moderation.”

Other takeaways from the report: Vigorous exercise lowered the risk of developing breast cancer by 17% in pre-menopausal women and 10% in post-menopausal women compared with women who were the least active.

Even general physical activity, such as gardening, helps. Post-menopausal women who were active were linked to a 13% lower risk of developing breast cancer, whereas there was no statistically significant benefit for pre-menopausal women.

The difference between the benefits of exercise for pre and post-menopausal women surprised Therese Bevers, medical director of the cancer prevention center at MD Anderson Cancer Center in Houston. “I even found myself giving a different recommendation yesterday to one of my patients who is pre-menopausal,” said Dr. Bevers. She told the patient that it’s really vigorous exercise that is linked to reducing the risk of breast cancer whereas moderate exercise may not confer the same benefit.

Being overweight or obese was associated with a greater risk of breast cancer in post-menopausal women, according to the study. Dr. McTiernan said each five unit increase in body-mass index was associated with a 12% increased risk.

Surprisingly, in pre-menopausal women, overweight and obese women had a decreased risk of developing breast cancer with each five unit increase in BMI resulting in a 18% reduced risk. But experts say that does not translate into recommending weight gain for such women, which comes with increased risks for many other health conditions.
Write to Sumathi Reddy at sumathi.reddy@wsj.com

How Exercise May Lower Cancer Risk

Gretchen Reynolds on the science of fitness.

The relationship between exercise and cancer has long both intrigued and puzzled oncologists and exercise physiologists.

Exercise is strongly associated with lowered risks for many types of cancer. In epidemiological studies, people who regularly exercise generally prove to be much less likely to develop or die from the disease than people who do not. At the same time, exercise involves biological stress, which typically leads to a short-term increase in inflammation throughout the body. Inflammation can contribute to elevated risks for many cancers.

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Now, a new study in mice may offer some clues into the exercise-cancer paradox. It suggests that exercise may change how the immune system deals with cancer by boosting adrenaline, certain immune cells and other chemicals that, together, can reduce the severity of cancer or fight it off altogether.

To try to better understand how exercise can both elevate inflammation and simultaneously protect the body against cancer, scientists at the University of Copenhagen in Denmark and other institutions decided to closely examine what happens inside mice at high risk for the disease.

So, for the new study, which was published this month in Cell Metabolism, they began by gathering a group of adult lab mice. These animals generally like to run. 

The scientists then implanted melanoma skin cancer cells into the mice before providing half of them with running wheels in their cages while the other animals remained sedentary. After four weeks, far fewer of the runners had developed full-blown melanoma than the sedentary mice and those that had been diagnosed with the disease showed fewer and smaller lesions. They also were less prone to metastases, even if scientists injected some of the cancer cells into their lungs to stimulate metastases. 

In effect, running seemed to have at least partially inoculated the mice against the cancer. 

Next, the scientists undertook the far more challenging task of reverse-engineering the process by which exercise might be helping to fight off the tumors. To start, they drew blood from both the exercising and sedentary animals and cells from any tumors in both groups. Then they looked microscopically at how the various samples were different. 

As expected, they found much higher levels of the hormone adrenaline in the blood of the exercising animals, especially right after they had been working out on the wheels but also at other times of the day. The body releases adrenaline in response to almost any type of stressful experience, including exercise. 

They also found higher levels of interleukin-6 in the blood of the runners. This is a substance that is released by working muscles and is believed to both increase and decrease inflammation in the body capriciously, depending on where and how it goes to work. 

Perhaps most important, they found much higher numbers in the bloodstreams of runners than in the sedentary mice of a type of immune cell named natural killer cells that are known to be potent cancer fighters. 

Somehow, the scientists speculated, these elements in the runners — their elevated adrenaline, IL-6, and natural killer immune cells and their lower cancer risk — must be entwined, but it wasn’t clear how. 

So the scientists repeated their original experiment multiple times, inducing cancer while allowing some mice to run and others to sit. But in some of these follow-up experiments, they injected the runners with a substance that blocked the production of adrenaline and gave sedentary animals large doses of added adrenaline. 

Then they again looked at the animals’ blood and other cells. 

What they now saw was that when running mice could not produce adrenaline, they developed cancer at the same rate as the sedentary animals, while the sedentary animals that had been injected with extra adrenaline fought off their tumors better than other sitting mice.

More remarkably, by studying the action of various genes within the cells of the mice, the scientists determined that adrenaline seemed to be sending biochemical signals to some of the animals’ IL-6 cells, making them physiologically more alert, so that when a tumor began to develop in the affected animal, those IL-6 cells in turn activated the natural killer cells in the bloodstream and actually directed them to the tumors, like minute guide fish.

Because the runners’ blood generally contained more adrenaline, more IL-6, and more natural killer cells than did the blood of the sedentary mice, this process was intensified. A larger number of natural killer cells were directed to tumors in the runners, allowing their immune systems, it seems, to more effectively combat the malignancy. 

With these results, “we show that voluntary wheel running in mice can reduce the growth of tumors, and we have identified an exercise-dependent mobilization of natural killer cells as the underlying cause of this protection,” said Pernille Hojman, a researcher at the University of Copenhagen who oversaw the new study. 

But mice, obviously, are not people, and it is impossible to know from this study whether a similar process occurs in humans, although exercise, particularly moderately intense exercise such as jogging, has been shown to increase adrenaline and the production of natural killer immune cells in people, Dr. Hojman said. 

“So the mechanisms,” she said, that seemed to partially protect the running mice in this study from malignancies, “can also happen in people,” perhaps providing one more incentive, if we still need it, to get up and move. 

General Soreness After Class

Make yourself a priority: You want to get in shape, and you want a better body. Perhaps you just want to be healthy. Whatever your reason for exercise, don’t let the effects of muscle soreness slow you down. At the same time, this soreness is a way of your body telling you something. Protein and a proper diet consisting of the right foods also aid in the dissipation of soreness. Stay on track and keep to your plan.

Drink plenty of water: Most of America is dehydrated. Studies show that up to 75% of America doesn’t drink enough water. Your muscles need water, especially when they are sore.

Stretch: Your muscles need to be stretched back to their normal length. Warming up the muscles properly and then stretching before physical activity is a superb way to prevent most muscle soreness.

Keep to our routine: Even if you’re sore stick to your routine.  Come to the studio as you normally would and use the time as a recovery ride.

Butt Soreness:  Soreness for the saddle is so common and there are a few ways to deal with it.

• Wear padded cycling specific shorts.
• Keep a fair amount of resistance on the bike to avoid bouncing in the saddle.
• Ask us to take a look at your seat adjustment.
• Do not avoid the the RYDE. The more you stay in the saddle the faster the discomfort will go away.

5 Way to Make the Most of your Velocity Ryding Experience

Vary the intensity: When you start out, it is best to begin with a low-intensity workout. However, as you build your endurance, you should up the intensity of your workout. You will see better results, especially in terms of weight loss with varying from moderate to high intensity aerobic workouts.

Vary your workout length: You don’t need to work out in 60 minutes (Standard Class) chunks every time. Occasionally it is beneficial to vary the length of your work out at a higher intensity 30 minutes (Xpress Class) or at lower intensities for 90 minutes (combine Standard and Xpress Class).

Stay hydrated: Make sure you are getting plenty of water throughout the day. Drinking a great deal just before you exercise is not the best option, since it can take two hours for your body to absorb the water. You can take sips throughout your workout, though. But your best bet is to get in the habit of drinking water throughout the day.

Don’t neglect the protein: Many people forget the importance of protein. If you are working out, you need to have the amino acids that provide building blocks for muscles. While you don’t need to eat a ton of protein, you should make sure you are getting some from lean sources, like legumes, fish and chicken. You can also get protein from shakes.

Eat carbs: If you want the energy to do workouts that are more effective, you need carbs. This doesn’t mean that your workout will be enhanced by a bunch of sugar, though. Good nutrition from carbs means focusing on fruits and vegetables and whole grains for most of your carb sources. If you drink a protein shake, add a banana, which is a great source of healthy carbs.