title: Candidate mechanisms accounting for effects of physical activity on breast carcinogenesis.
abstract: Evidence is strong that a reduction in risk for breast cancer is associated with moderate to vigorous physical activity (PA); however, there is limited understanding of the role of type, intensity, duration, and frequency of PA and their mechanisms in accounting for this health benefit. The objective of this review is to stimulate investigations of candidate mechanisms that may account for the effects of the intensity and duration of aerobic PA on breast cancer risk and tumor burden. Three hypotheses are considered: 1) the mTOR network hypothesis: PA inhibits carcinogenesis by suppressing the activation of the mTOR signaling network in mammary carcinomas; 2) the hormesis hypothesis: the carcinogenic response to PA is nonlinear and accounted for by a physiological cellular stress response; and 3) the metabolic reprogramming hypothesis: PA limits the amount of glucose and glutamine available to mammary carcinomas thereby inducing apoptosis because tumor-associated metabolic programming is reversed. To link these hypotheses to systemic effects of PA, it is recommended that consideration be given to determining: 1) what contracting muscle releases into circulation or removes from circulation that would directly modulate the carcinogenic process in epithelial cells; 2) whether the effects of muscle contraction on epithelial cell carcinogenesis are exerted in an endocrine, paracrine, autocrine, or intracrine manner; and 3) if the effects of muscle contraction on malignant cells differ from effects on normal or premalignant cells that do not manifest the hallmarks of malignancy.
authors: Cancer Prevention Laboratory, Colorado State University, Fort Collins, CO 80523, USA. henry.thompson@colostate.edu
authors: Henry J
authors: HJ
authors: Thompson
authors: Weiqin
authors: W
authors: Jiang
authors: Zongjian
authors: Z
authors: Zhu
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D015444:Exercise; D005260:Female; D006801:Humans