Does exercise help prevent breast cancer?

A new federally funded University of Pennsylvania School of Medicine study aims to learn whether women at high risk of breast cancer can use exercise to meaningfully reduce their risk of getting the disease.

Building on evidence that reducing estrogen in the body reduces cancer risk, and that elite female athletes experience a drop in estrogen levels that often cause them to stop ovulating and menstruating, the WISER Sister trial will investigate two different levels of regular treadmill exercise as a possible intervention for breast cancer risk reduction.

The stakes for women who carry BRCA genetic mutations are high - as many as 80 percent of them will develop breast or ovarian cancer during their lives - but options for risk reduction are drastic and few, and the choices may be unacceptable to some women. Previous Penn research shows that prophylactic mastectomy slashes carriers' breast cancer risk by 90 percent, while prophylactic oophorectomy, or ovary removal, halves their breast cancer risk and reduces their chances of getting of ovarian cancer by about 85 to 90 percent. Though the surgeries are highly effective, they usher in quality of life concerns - particularly with regard to body image and sexuality - and the early menopause that results from ovary removal brings a woman's childbearing years to an end. And the procedures aren't recommended for women who have a family history of breast cancer but don't carry the mutated genes.

"The decision to have these surgeries is so difficult that many women delay them, sometimes with terrible consequences. We would like to find out if exercise could buy high-risk women time they need to more safely think through their options," says Kathryn Schmitz, PhD, MPH, an assistant professor in the Center for Clinical Epidemiology and Biostatistics who is leading the new study, in partnership with Susan Domchek, MD, director of the Abramson Cancer Center's Cancer Risk Evaluation Program. "Exercise also has a number of health and stress reduction benefits that make it even more attractive for this population."

Over the next three years, Schmitz's team will enroll 160 women ages 18 to 40, who must have an elevated risk of getting breast cancer based on her family history of the disease. BRCA carriers will be included among eligible women. However, participants will not be required to undergo genetic testing.

Previous research on estrogen exposure strongly suggests that reducing estrogens will result in reduced breast cancer risk in this population. The investigators plan to use their findings to offer effective exercise guidelines for high-risk women. Unlike surgery, exercise is a low-cost intervention with few side effects, so Schmitz is hopeful that the study results will offer risk-reduction tools to a larger swath of high-risk women, including minorities and other groups that may be underserved or lack access to genetic testing or proper early screening.

"We are interested in rigorously investigating all potential options to decrease cancer risk," says Domchek, an associate professor of Medicine in the division of Hematology/Oncology. "Exercise is a wonderful intervention due to its numerous health benefits. However, it is important for us to quantify the amount of exercise needed and the potential benefits such exercise might provide."

Although it is unknown how much the exercise interventions tested in the trial will reduce estrogen exposure, Schmitz says even evidence of marginal risk reduction -- that exercise may help delay breast cancer onset, decrease breast density to improve the accuracy of early screening tests, or result in smaller tumors -- could be of help to women planning risk reduction strategies during their 20s and 30s.

Trial participants will be placed into three randomized groups who will be followed for seven months. Each participant will receive a treadmill to use at home, which she will get to keep after the study is over. A "low dose" group will complete 150 minutes of exercise each week, the same amount recommended for general health and fitness, while a "high dose" group will do 300 minutes of exercise each week, similar to the workouts recommended for weight control. A third group, serving as the control, will continue doing their usual activities for the duration of the study and will receive the treadmill at the end of study completion.

Each woman will give daily urine samples at points during the trial, which will allow investigators to measure their levels of estrogen, progesterone and other sex hormones. The women's body composition will also be measured, and they will receive breast MRIs at no cost to them before and after the study to examine changes in the density of their breast tissue.

"It is frightening to face high risk for breast cancer at a young age. Most of us think of cancer as something that happens later in life. Young women may not even want to approach the issue of getting genetic testing yet, but may want to do something. The WISER Sister study offers those women an option," Schmitz says. "The benefits of the study will have a ripple effect to other good health habits, too, by helping women adopt a regular exercise regimen."

The WISER (Women in Steady Exercise Research) Sister trial is funded by a grant from the National Cancer Institute, which is part of the U.S National Institutes of Health.

PENN Medicine is a $3.6 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is currently ranked #4 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,700 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System (UPHS) includes its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's top ten "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center. In addition UPHS includes a primary-care provider network; a faculty practice plan; home care, hospice, and nursing home; three multispecialty satellite facilities; as well as the Penn Medicine at Rittenhouse campus, which offers comprehensive inpatient rehabilitation facilities and outpatient services in multiple specialties.

The Abramson Cancer Center (ACC) of the University of Pennsylvania is a national leader in cancer research, patient care, and education. The pre-eminent position of the Cancer Center is reflected in its continuous designation as a Comprehensive Cancer Center by the National Cancer Institute for 30 years, one of 39 such Centers in the United States. The ACC is dedicated to innovative and compassionate cancer care. The clinical program, composed of a dedicated staff of physicians, nurse practitioners, nurses, social workers, physical therapists, nutritionists and patient support specialists, currently sees over 50,000 outpatient visits, 3400 inpatient admissions, and provides over 25,000 chemotherapy treatments, and more than 65,000 radiation treatments annually. Not only is the ACC dedicated to providing state-of-the-art cancer care, the latest forms of cancer prevention, diagnosis, and treatment are available to our patients through clinical themes that developed in the relentless pursuit to eliminate the pain and suffering from cancer. In addition, the ACC is home to the 400 research scientists who work relentlessly to determine the pathogenesis of cancer. Together, the faculty is committed to improving the prevention, diagnosis and treatment of cancer.