Research: Most-Effective Breast Cancer Treatment Should Address Obesity, Integrate Exercise

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Yale cancer scientist Melinda Irwin says that the connection between obesity and cancer are so strong — as are recent findings about the effectiveness of exercise and diet in treating cancer — that pharmaceutical companies should be required to include these two lifestyle components in drug trials.

A mandate is needed, Irwin said, because the pharmaceutical industry, which funds most large-scale drug trials, “has no incentive to fund lifestyle behavioral interventions. Why would they? There’s no pill to take.”

Irwin studies the effects of weight loss and exercise on breast cancer survivors. Her comments echo those by the American Society of Clinical Oncology, which has issued a new position paper calling obesity “a major unrecognized risk factor for cancer.’’

“As many as 84,000 cancer diagnoses each year are attributed to obesity, and overweight and obesity are implicated in 15 percent to 20 percent of total cancer-related mortality,” the group says in its position paper published in the online version of the Journal of Clinical Oncology Oct. 1. It calls for medical school curriculums to be revamped to teach oncologists how to help their patients “lose weight and make other healthy lifestyle changes.”

The National Cancer Institute says obesity is linked to poorer outcomes in cancer patients, undercuts the effectiveness of drugs to treat cancer and may increase a patient’s risk of developing new cancers and other diseases. Obesity has been associated with greater risks of postmenopausal breast cancer and colon cancer and cancers of the prostate, kidney, pancreas, esophagus, gallbladder and others.

Exercise Is A ‘Stepchild’ To Weight And Diet

Medical advances in breast cancer treatment over the past 30 years have spurred some researchers to focus now on how to keep the increasing numbers of survivors healthy.

Melinda Irwin in her office at Yale.

Jenifer Frank Photo

Melinda Irwin in her office at Yale.

Earlier in her career, Irwin studied cancer prevention, finding that moderate physical activity decreased levels of estrogen, a hormone that can be associated with breast cancer, by about 10 percent, an outcome she calls “totally significant.”

Since then, Irwin, the co-program leader of Cancer Prevention and Control Research at the Yale Cancer Center, has focused on breast cancer survivors who are overweight and obese, also doing some research into patients with ovarian cancer.

In 2008, she published the Yale Exercise and Survivor Study (YES), which looked at the effect of aerobic exercise – in this case, brisk walking – on levels of insulin and “insulin-like growth factors” (IGF) in postmenopausal breast cancer survivors. Insulin and IGF can be signs, or “biomarkers,” of increased risk of breast cancer.

The study showed that the women who exercised moderately – about 30 minutes of walking five days a week – had lower insulin rates than the more sedentary group.

The following year, in a second YES study, Irwin examined the effects of moderate exercise on body composition, including weight and bone mineral density, among breast cancer survivors. Breast cancer survivors often gain weight, partly as a result of their treatment. Also, they are often more vulnerable to bone fractures, because the cancer drugs decrease bone mineral density.

This second YES study showed positive changes in body composition among the women who participated in moderate aerobic exercise.

“I was always interested in exercise because it’s always sort of a stepchild to weight and diet,” Irwin said. “You always hear about weight and diet, and exercise is never really considered. And yet there are significant direct effects of exercise, independent of body weight, or BMI [body mass index], on certain outcomes.”

She said breast cancer survivors who were exercising a few years after their diagnosis “had about a 50 percent lower risk of recurrence or mortality, compared to those not exercising.”

In her recent study called LEAN – Lifestyle, Exercise And Nutrition – Irwin and her colleagues looked at the effect of these factors in 100 obese or overweight breast cancer survivors, noting that more than 65 percent of breast cancer patients gain weight because of chemotherapy.

“There’s pretty consistent literature showing that obesity at time of diagnosis is associated with breast cancer recurrence and mortality,” Irwin said. Obese cancer survivors face about a 33 percent higher risk of a recurrence or of dying from breast cancer compared to survivors who are of normal weight.

“Unfortunately, though, it’s not just obesity at diagnosis but weight gain that may occur after diagnosis,” Irwin said. “So that weight gain … can put you at even increased risk of recurrence or mortality.”

The LEAN study found that a 6 percent weight loss, through exercise and diet, led to a 30 percent decrease in the women’s levels of a protein associated with breast cancer. And, “being physically active after a breast cancer diagnosis is associated with a 30 percent to 40 percent lower risk of breast cancer recurrence and mortality,” she wrote.

Irwin is expanding the LEAN study to another 100 breast cancer survivors. In this study, breast tissue will be collected after the lifestyle interventions, the first time this has been done, she said.

Cancer Doctors And Funding Are Key

Surgery, chemotherapy and radiation are now doctors’ tools for fighting breast and other cancers. Irwin hopes that exercise and weight management become full partners with those treatments in the recovery from breast cancer.

But many oncologists, and health-insurance companies, are not yet convinced of “the benefit of weight management and lifestyle change,” Irwin said. This is so even though “the mechanistic pathways of how lifestyle behavior change … are similar to how certain drugs work,” she said.

A spokeswoman for pharmaceutical giant Pfizer had a brief response to Irwin’s comment about drug companies’ lack of incentive to include lifestyle changes in their drug trials: “It’s our job to discover and develop innovative therapies that significantly impact human health.”

To encourage exercise and diet changes to patients, the national society of oncologists calls the period right after an individual is diagnosed with cancer a “teachable moment,” when that person is more willing to adopt more healthy behavior in terms of diet and exercise. At that point, the patient’s oncological team “is in a unique position to help patients lose weight and make other healthy lifestyle changes.”

Irwin is seeking volunteers for her 2nd LEAN study — lifestyle, exercise and nutrition — through 2015. If you think you may be interested, call her at 203-645-5995.





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