Changes in estrogen breakdown, or metabolism, may be one of the mechanisms by which aerobic exercise lowers a woman?s breast cancer risk. A study discussing data that suggests that exercise influences estrogen metabolism was published earlier today in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

Exercise boosts the immune system and helps keep a persons weight in check. Experts suggests that as little as three hours of exercise per week, or about 30 minutes a day, can help women lower her risk of breast cancer. These fact have been presented in a number of studies. However, until now, the clinical proof and the understanding of the mechanism of action have been missing.

?Observational studies suggest physical activity lowers breast cancer risk, but there are no clinical studies that explain the mechanism behind this,? noted Mindy S. Kurzer, Ph.D., (photo) professor in the Department of Food Science and Nutrition at the University of Minnesota in Saint Paul. Kurzer holds a joint appointment in the Division of Hematology, Oncology and Transplantation in the Department of Medicine. ?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.?

WISER-trial
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. [1][2][3][4]

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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.

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Eighty-six percent of participants from the control group and 78% from the intervention group completed the study.

Estrogen-metabolism
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.

“Good” vs. “Bad”
The researchers 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,? Kurzer explained. ?It is very important, however, to decipher the biological mechanisms behind this phenomenon.?

Other studies
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.

For more information
[1]Smith AJ, Phipps WR, Thomas W, Schmitz KH, Kurzer MS. The Effects of Aerobic Exercise on Estrogen Metabolism in Healthy Premenopausal Women.Cancer Epidemiol Biomarkers Prev May 2013 22; 756. doi: 10.1158/1055-9965.EPI-12-1325. [Abstract]
[2] Tehard B, Friedenreich CM, Oppert JM, Clavel-Chapelon. Effect of physical activity on women at increased risk of breast cancer: results from the E3N cohort study. Cancer Epidemiol Biomarkers Prev. 15(1):57-64, 2006.
[3] Peters TM, Schatzkin A, Gierach GL, et al. Physical activity and postmenopausal breast cancer risk in the NIH-AARP diet and health study. Cancer Epidemiol Biomarkers Prev. 18(1):289-96, 2009.
[4] Eliassen AH, Hankinson SE, Rosner B, Holmes MD, Willett WC. Physical activity and risk of breast cancer among postmenopausal women. Arch Intern Med. 170(19):1758-64, 2010.

Clinical trial
NCT00393172 – Women in Steady Exercise Research [Formerly Women, Oxidative Stress, Exercise and Estrogens (WOSEE)] (WISER).

Photo courtesy: Regents of the University of Minnesota.

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