Aerobic exercise may reduce a woman’s breast cancer risk by altering estrogen metabolism to produce more of the metabolites that keep the disease from developing, researchers have learned.

Although it is well accepted that exercise can lower the risk of breast cancer, no clinical studies explain the mechanism behind this relationship. To investigate the effects of exercise on premenopausal estrogen metabolism pertinent to breast cancer risk, Mindy S. Kurzer, PhD, of the Department of Food Science and Nutrition at the University of Minnesota in St. Paul, Minnesota, and colleagues randomized 391 sedentary, healthy, young, premenopausal women to an exercise intervention or a control group.

As Kurzer’s group explained in the American Association for Cancer Research (AACR) journal Cancer Epidemiology, Biomarkers & Prevention (2013;22[5]:756-764), the 212 women in the exercise group engaged in 30 minutes of moderate-to-vigorous aerobic exercise on a treadmill, stair-stepper, or elliptical machine five times per week for approximately 16 weeks. The 179 remaining women continued a sedentary lifestyle for the entire study period.

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The investigators used liquid chromatography/tandem mass spectrometry to measure urinary levels of the parent estrogens estrone (E1), estradiol, and estriol, as well as nine of their metabolites, at baseline and at the end of the study. As Kurzer explained in a statement from the AACR, estrogen metabolism favoring the production of the metabolite 2-hydroxyestrone (2-OHE1) over the metabolite 16α-hydroxyestrone (16α-OHE1) has been associated with reduced breast cancer risk.

The exercise intervention resulted in significant increases in aerobic fitness and lean body mass and a significant decrease in body-fat percentage among the 165 women in that group who completed the study. In addition, the ratio of 2-OHE1 to 16α-OHE1 increased significantly among the exercisers.

No ratio change was seen among the 153 control group members who completed the study, but E1 decreased significantly in these participants. The change from baseline in the 2-OHE1/16α-OHE1 ratio differed significantly between the exercisers and the control subjects even after adjustment for baseline values.

These findings led Kurzer and coauthors to conclude that changes in premenopausal estrogen metabolism may be a mechanism by which increased physical activity lowers a woman’s risk for breast cancer.