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.; Bhanot, U.; Linkov, I.; Jain, M.; Jochelson, M. S.; Monetti, M.; Seewaldt, V. L; Pilewskie, M. L.; Pribil, P.; Zhu, C.; Arbet, J.; Mangino, D. A.; Boutros, P. C. |
| 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: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2025-08-15 |
| Start Page: | 3377 |
| End Page: | 3387 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-24-4298 |
| PUBMED: | 40184238 |
| PROVIDER: | scopus |
| PMCID: | PMC12353064 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author Lee W. Jones -- Source: Scopus |
