Physical activity as a negative modulator of estrogen-induced breast cancer.

Physical activity is a protective factor for breast cancer. Exposure to estrogen is an important determinant of breast cancer risk and exercise reduces estrogen levels, with the level of evidence being stronger for post-menopausal women. Possible mechanisms for estrogen induced breast cancer include increased breast epithelial cell proliferation, the metabolism of estrogen to genotoxic metabolites, such as DNA-adducts, and the silencing of tumor suppressor genes (TSGs) that have been implicated in breast carcinogenesis by inducing gene promoter hypermethylation, which is potentially reversible. Animal studies suggest that physical activity decreases breast tumor growth by promoting changes in cellular proliferation and apoptosis. Human studies provide some support for exercise producing favorable changes in estrogen metabolism that may lead to reduced breast epithelial cell proliferation. No studies have been performed to determine whether exercise decreases the accumulation of estrogen metabolite DNA-adducts in breast tissue. However, research supports the hypothesis that physical activity reduces promoter hypermethylation of TSGs implicated in breast carcinogenesis by lowering circulating estrogen levels. Thus, further research is necessary to clarify the mechanisms that relate to physical activity as a negative modulator of breast cancer risk to develop meaningful guidelines for the use of physical activity in breast cancer prevention.