Pre-tumor exercise decreases breast cancer in old mice in a distance-dependent manner

Epidemiological evidence supports a protective effect of physical activity for breast cancer but pre-clinical studies are needed to help define the underlying mechanisms in an age-related manner. We utilized 18-month old BALB/c mice injected in the mammary fat pad with syngeneic 4T1 tumor cells as a model of invasive breast cancer. A negative correlation was observed between daily distance ran, prior to tumor injection, and absolute tumor mass measured at necropsy (Pearson's r = -0.89, P = 0.0066, R(2) = 0.80). A correlation was also observed between distance ran before tumor implant and the histological score for mitotic index (Pearson's r = -0.85, P = 0.034, R(2) = 0.72). Runners showed an increased respiratory exchange ratio during the light cycle (P = 0.029) suggesting that voluntary running shifted resting substrate metabolism toward glucose oxidation, relative to lipid oxidation. The shift in substrate metabolism was significantly different from baseline for both groups of animals, indicating that the tumor burden might have been responsible. The observations from this study indicate that running longer distances is associated with decreased breast tumor burden in old mice, suggesting that physiological factors generated by exercising before tumor onset are protective against tumor progression. The mechanisms for this protective effect are not known but the data show that older mice are useful models to address specific questions in cancer research and support further studies on the ability of exercise training to protect older women at risk for breast cancer.