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


Authors: Jones, L. W.; Lavery, J. A.; Tsai, B. L.; Moskowitz, C. S.; Lee, C. P.; Harrison, J.; Michalski, M. G.; Stoeckel, K.; Graham, C.; Iyengar, N. M.
Article Title: 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. Patients and Methods: In a phase I randomized trial, 75 non-exercising 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 pre-clinical 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 min-utes/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. © 2025 Elsevier B.V., All rights reserved.
Keywords: adult; controlled study; human tissue; aged; middle aged; human cell; clinical trial; hypertension; ki 67 antigen; cell proliferation; ki-67 antigen; mouse; animal; metabolism; animals; mice; breast cancer; randomized controlled trial; clinical assessment; body weight; pathology; breast neoplasms; proteomics; risk factor; biopsy; ultrasound; physiology; health care; biological activity; blood analysis; breast tumor; hyperplasia; diabetes mellitus; physical activity; high performance liquid chromatography; phase 1 clinical trial; randomization; cardiopulmonary exercise test; electrocardiogram; hyperlipidemia; prevention and control; kinesiotherapy; epithelial mesenchymal transition; exercise therapy; lobular carcinoma; procedures; preclinical study; physiological stress; very elderly; humans; human; female; article; epithelial cell line; lunar dpx; mac 5000; sciex zenotof 7600
Journal Title: Clinical Cancer Research
Volume: 31
Issue: 16
ISSN: 10780432
Publisher: Elsevier B.V.  
Date Published: 2025-01-01
Start Page: 3377
End Page: 3387
Language: English
DOI: 10.1158/1078-0432.Ccr-24-4298
PUBMED: 40184238
PROVIDER: scopus
DOI/URL:
Notes: Article -- Source: Scopus
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