A Co-clinical Trial of Exercise Therapy in Breast Cancer Prevention.

PURPOSE: We conducted a mouse-human co-clinical trial to evaluate the biological efficacy of exercise therapy in breast cancer prevention. PATIENTS AND METHODS: In a phase I 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 effect 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 (SD) 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 is 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 a marked reduction in genes involved in epithelial-mesenchymal transition in the 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). CONCLUSIONS: Exercise therapy is a promising strategy for the early interception of breast cancer in high-risk women. See related commentary by McTiernan, p. 3353.