A Co-Clinical Trial of Exercise Therapy in Breast Cancer Prevention

Abstract Purpose. We conducted a mouse–human co-clinical trial to evaluate the biological efficacy of exercise therapy in breast cancer prevention. Materials and methods. In a phase 1 randomized trial, 75 nonexercising women at high-risk of breast cancer were allocated to receive (1:1 ratio): usual care or one of three exercise therapy dose regimens: 75, 150, or 300 minutes/week for 24 consecutive weeks. Biological efficacy was evaluated by changes in breast epithelial cell proliferation (Ki67). Correlative proteomic analysis of paired tissue and plasma samples was also performed. A corresponding preclinical study tested the dose-response of exercise therapy on breast tumor latency. Results. Change in Ki67 was not different between groups (global p-value = 0.2). Among participants with paired Ki67 measures, the mean (s.d) change in Ki67 was: –1.26 (4.32) for 75 minutes/week, –1.74 (5.04) for 150 minutes/week, –0.45 (5.16) for 300 minutes/week, and 3.40 (5.53) for usual care (global p-value = 0.04). Only 150 minutes/week associated with significant reductions in Ki67 compared with usual care (Bonferroni-adjusted p-value 0.03). The “response rate” (reduction in Ki67) was 29% for usual care compared with 52% for 150 minutes/week. Proteomics revealed marked reduction in genes involved in epithelial mesenchymal transition in tissues of responding patients. In the preclinical study, only 150 minutes/week significantly delayed tumor latency compared with control (Benjamini- Hochberg-adjusted p-value 0.02). Conclusion. Exercise therapy is a promising strategy for early interception of breast cancer in high-risk women.