Aerobic Training-Induced Host Changes Alter Breast Cancer Cell Phenotypes and Tumor Progression

Abstract

A growing number of studies have investigated the role of exercise both during and after a breast cancer diagnosis. Observational data suggests that regular endurance exercise is associated with a 20-50% reduction in cancer-specific mortality in women diagnosed with early stage breast cancer, compared to inactive women; however it is unclear whether there is a differential association across breast cancer subtypes. As a pre-requisite to guide future large phase II/III clinical trials, there is a critical need to confirm the biological plausibility of the exercise association in breast cancer patients as well as elucidate the underlying mechanisms of action via utilization of preclinical models. In the present study we investigated the systemic effects of prescribed aerobic training in cancer patients and the direct impact on breast cancer cell subtype phenotypes. In order to test the in vivo significance, we interrogated aerobic training effects on breast cancer progression and tumor biology using syngeneic breast cancer mouse models. Our results suggest that aerobic training may alter the host availability of pro-inflammatory and growth factor cytokines in patients with solid tumors. Modulation of systemic effectors in breast cancer patients compared to controls causes a differential phenotypic response on breast cancer cell subtypes. In vivo, aerobic training has a differential response on breast tumor progression compared to controls that is mediated by Hif1-α and metabolic reprogramming of breast cancer cells.