Exercise-related changes in estrogen metabolism may lower breast cancer risk
Changes in estrogen breakdown, or metabolism, may be one of the mechanisms by which aerobic exercise lowers a woman’s breast cancer risk, according to data published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.
“Observational studies suggest physical activity lowers breast cancer risk, but there are no clinical studies that explain the mechanism behind this,” said Mindy S. Kurzer, Ph.D., professor in the Department of Food Science and Nutrition at the University of Minnesota in Saint Paul. “Ours is the first study to show that aerobic exercise influences the way our bodies break down estrogens to produce more of the ‘good’ metabolites that lower breast cancer risk.”
Kurzer and her colleagues conducted the Women in Steady Exercise Research (WISER) clinical trial, which involved 391 sedentary, healthy, young, premenopausal women. They randomly assigned the women to two age-matched, body mass index-matched groups: a control group of 179 women and an intervention group of 212 women.
While women in the control group continued a sedentary lifestyle for the entire study period, women in the intervention group performed 30 minutes of moderate-to-vigorous aerobic exercise five times a week for 16 weeks. Aerobic exercises included the treadmill, stair stepper or elliptical machine. The researchers adjusted the workout intensity for each individual so that the maximal heart rate was uniform among all participants.
Eighty-six percent of participants from the control group and 78 percent from the intervention group completed the study.
The researchers collected 24-hour urine samples on three consecutive days prior to study initiation and on three consecutive days at the end of the study. Using a state-of-the-art technique called liquid chromatography/tandem mass spectroscopy, they measured the amount of three parent estrogens, E1, E2 and E3, and nine of their breakdown products called metabolites, in the participants’ urine samples. According to Kurzer, estrogen metabolism favoring the production of a metabolite called 2-hydroxyestrone (2-OHE1) over one called 16alpha-hydroxyestrone (16alpha-OHE1), which results in an increase in the 2-OHE1/16alpha-OHE1 ratio, has been linked with a reduction in breast cancer risk.
Breast cancer risk reduced 30 percent in women who exercise 10 hours per week
Women may significantly reduce their risk for breast cancer by exercising a couple hours each day, a new study finds. The study found that even mild physical activity like walking reduced risk for the disease that strikes 227,000 new women each year.
For the study, researchers at the University of North Carolina at Chapel Hill compared 1,500 women with breast cancer to more than 1,550 women without breast cancer who were part of the ongoing “Long Island Breast Cancer Study Project” that looked at environmental causes of the disease.
The researchers found that women who exercised during their reproductive years or following menopause reduced their risk of developing breast cancer. The greatest risk reduction was found in women who exercised 10 to 19 hours per week (or two hours each day for five days), but a woman’s risk was reduced for all levels of exercise intensity, even light. Exercise appeared to reduce the risk of hormone receptor positive breast cancers, which are the most commonly diagnosed tumors among U.S. women.
Risk factors you cannot change
Gender
Simply being a woman is the main risk factor for developing breast cancer. Men can develop breast cancer, but this disease is about 100 times more common among women than men. This is likely because men have less of the female hormones estrogen and progesterone, which can promote breast cancer cell growth
Aging
Your risk of developing breast cancer increases as you get older. About 1 out of 8 invasive breast cancers are found in women younger than 45, while about 2 of 3 invasive breast cancers are found in women age 55 or older.
Genetic risk factors
About 5% to 10% of breast cancer cases are thought to be hereditary, resulting directly from gene defects (called mutations) inherited from a parent. See the section, “Do we know what causes breast cancer?” for more information about genes and DNA.
BRCA1 and BRCA2: The most common cause of hereditary breast cancer is an inherited mutation in the BRCA1 and BRCA2 genes. In normal cells, these genes help prevent cancer by making proteins that keep the cells from growing abnormally. If you have inherited a mutated copy of either gene from a parent, you have a high risk of developing breast cancer during your lifetime. The risk may be as high as 80% for members of some families with BRCA mutations. These cancers tend to occur in younger women and more often affect both breasts than cancers in women who are not born with one of these gene mutations. Women with these inherited mutations also have an increased risk for developing other cancers, particularly ovarian cancer.
In the United States BRCA mutations are more common in Jewish women of Ashkenazi (Eastern Europe) origin than in other racial and ethnic groups, but they can occur in any racial or ethnic group.
Changes in other genes: Other gene mutations can also lead to inherited breast cancers. These gene mutations are much rarer and often do not increase the risk of breast cancer as much as the BRCA genes.
“The observation of a reduced risk of breast cancer for women who engaged in exercise after menopause is particularly encouraging given the late age of onset for breast cancer,” study author Lauren McCullough, a doctoral candidate at UNC’s Gillings School of Public Health, said in a news release. The results were published in the June 25 issue of the American Cancer Society’s journal, Cancer.
She and her colleagues found that aerobic exercise led to an increase in the amount of 2-OHE1 and a decrease in the amount of 16alpha-OHE1, which led to a significant increase in the 2-OHE1/16alpha-OHE1 ratio. There were no changes in the 2-OHE1/16alpha-OHE1 ratio in the urine of control group participants.
“Exercise, known to favor fitness and improve heart health, is also likely to help prevent breast cancer by altering estrogen metabolism,” said Kurzer. “It is very important, however, to decipher the biological mechanisms behind this phenomenon.”
In collaboration with researchers at the University of Pennsylvania in Philadelphia, Kurzer is conducting similar studies in women with a high risk for breast cancer.
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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.
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Jeremy Moore
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American Association for Cancer Research