Most people agree that physical fitness is good for one's overall health, but some researchers are taking that knowledge a step further and asking whether exercise can prevent cancer from developing or recurring. “I think a lot of people realize that physical activity is important for prevention of heart disease and diabetes, but I don't think it's common knowledge that it can affect cancer risk,” says I-Min Lee, ScD, professor of epidemiology at the Harvard School of Public Health in Boston, Massachusetts. Dr. Lee's research focuses primarily on the role of physical activity in promoting health and preventing chronic disease. She was the lead author of a study published last summer in The Lancet, which published a series of articles related to physical activity and health in conjunction with London's hosting of the 2012 Summer Olympic Games.1 Dr. Lee and her colleagues found that between 6% and 10% of the major chronic diseases worldwide were attributable to inactivity, including 10% of both colon and breast cancer cases. The World Health Organization (WHO) guidelines suggest 150 minutes per week of moderate to intense physical activity, such as walking at a brisk pace. Studies have found many people in the world are not meeting these guidelines, she says. “If everyone in the world were as active as these guidelines recommend, we could avoid about 5 million deaths–almost the same amount as if everyone stopped smoking,” Dr. Lee states, pointing out that approximately one-third of the world is inactive while approximately one-quarter of the world still smokes. “If people see that inactivity is as bad as smoking, hopefully they will become more concerned.” In the study, Dr. Lee and her colleagues focused specifically on breast cancer and colon cancer because they have been most convincingly related to inactivity, she says. They analyzed data from 122 countries worldwide to determine whether the WHO guidelines for physical activity were being met. Participants were surveyed by the WHO about what type of activities they did in their leisure time, household chores, jobs, and transportation. “Some studies have said that just doing any physical activity will help for cardiovascular health, but to reduce the risk of colon and breast cancer it appears you need to at least meet the current WHO recommendations,” Dr. Lee says. Among the possible reasons why physical activity is believed to be associated with a reduction in cancer risk is its apparent impact on levels of reproductive hormones and inflammatory markers, and levels of insulin and body fat, all of which have been linked to certain cancers. Dr. Lee also is involved with a study ancillary to the Women's Health Study that will provide an objective measure of physical activity levels in approximately 15,000 to 18,000 women by having them wear accelerometers attached to their hips. She anticipates the measurement phase will take another 2 years and eventually give investigators an opportunity to examine the impact of physical activity on chronic diseases and overall mortality. Meanwhile, researchers elsewhere are examining whether exercise actually can prevent disease recurrence in patients with cancer. The University of Arizona Cancer Center (UACC) in Tucson, for example, is leading a study into whether physical activity, combined with a healthy diet, can improve quality of life and prevent disease recurrence in women who are in clinical complete remission from advanced ovarian, peritoneal, or fallopian tube cancer. The study, known as LIvES (Lifestyle Intervention for Ovarian Cancer Enhanced Survival), is already underway and eventually will include 1070 recent survivors of stage II to IV ovarian cancer from among Gynecologic Oncology Group clinics across the country. Participants are randomly assigned to either the intervention or standard-care group. The latter will receive information concerning diet and physical activity and will have some coaching, but they will not receive the direct, intensive counseling that the intervention group does. Researchers use a combination of telephone and Web-based coaching software to contact participants a minimum of 22 times over the 2-year study period. The women are asked to complete questionnaires on their diet, physical activities, quality of life, and other health and lifestyle issues. Participants also will have blood samples taken. Coaches in the LIvES study contact participants via phone and the Web to discuss physical activity level. The LIvES study was the result of research such as the Women's Health Study, which demonstrated that a low-fat diet led to a greater than 40% reduction in the risk of developing ovarian cancer. Other published findings have indicated a 25% to 30% reduction in the risk of developing or having a recurrence of ovarian cancer in participants who follow the WHO guidelines, says David Alberts, MD, UACC director and LIvES cochair. As a specialist in the treatment of ovarian cancer, Dr. Alberts has a deep interest in finding new methods to prevent disease recurrence. Nearly 70% of patients with ovarian cancer will go into clinical complete remission after a recurrence but, unfortunately, approximately 75% of them will develop disease recurrence in 3 to 4 years, and many eventually die of the disease, he says. He adds that because investigators know that ovarian cancer is largely a Western disease (one that appears to have a high prevalence among women with sedentary lifestyles and who consume a diet high in dairy and red meat compared with other parts of the world), the study is particularly important. “To my knowledge, it's the only phase 3 trial in the United States looking at this combination of lifestyle factors in any tumor type,” he says. Another researcher, Lee W. Jones, PhD, associate professor of radiation oncology at the Duke Cancer Institute in Durham, North Carolina, has conducted a number of studies that focus on the role of exercise in mitigating cancer recurrence, as well as the acute and late effects of cancer therapy (such as cardiovascular injury). He and his colleagues published an article in the June 2011 issue of the Journal of Clinical Oncology that demonstrated an association between exercise and longer survival among patients with brain tumors.2 The study enrolled 243 patients with advanced recurrent gliomas. Typically, such patients have a median life expectancy of fewer than 6 months. The patients who reported participating in the equivalent of the WHO guidelines of moderate to intense exercise 5 days per week for 30 minutes lived a median of 21.84 months versus 13.03 months for the most sedentary patients. Although the results are promising, Dr. Jones cautions that this study, like many other epidemiological studies in this area, indicates an association between exercise and cancer survival, not a cause-and-effect relationship. “It might not be the exercise at all,” he says. “It's the first step of evidence needed to prove it's real.” He and his colleagues also have been researching their theories in mice, finding that if they exercise a mouse, the tumors grow approximately 30% slower. Nevertheless, they need to determine why and whether the same is true for humans. Dr. Jones believes that these and other questions need to be answered before a large, clinical trial should be undertaken. “Our approach is to try to find out why and how it works mechanistically,” he says. “We need to know who would benefit from exercise and the specific dose amount, and we're doing that in animal models first.” Others, like the UACC scientists, are already testing the theory in humans. And in Canada, Kerry Courneya, PhD, a professor and Canada Research Chair of physical activity and cancer at the University of Alberta in Edmonton, is coleading a large, randomized study to determine whether exercise can reduce disease recurrence in patients with colorectal cancer. Dr. Courneya's previous research showed that many of these patients are inactive and overweight. The study, known as the CHALLENGE (Colon Health and Life-Long Exercise Change) trial and undertaken by the National Cancer Institute of Canada Clinical Trials Group, will recruit approximately 1000 colon cancer survivors in Canada and Australia and support one-half of them in increasing their activity levels. The study also will examine whether exercise improves patients' quality of life. Researchers will follow the participants for 10 years. Dr. Jones notes that insurance does not cover exercise programs for cancer patients as it does for those with cardiovascular diseases. He considers it his job to provide evidence that may eventually change that scenario. “We need robust evidence,” he says. “Can cancer patients exercise safely? How much exercise can you prescribe and what type is most effective?” He describes research into exercise and cancer as “a field in motion.” Fifteen years ago, if you wanted to exercise a person with cancer, they'd think you were crazy,” he says. “It would be pretty amazing if we show exercise can keep cancer from recurring, and I think we'll see some major findings in the next 4 to 5 years.”