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Clin Cancer Res. 2019 Apr 24. doi: 10.1158/1078-0432.CCR-18-3143. [Epub ahead of print]

Impact of a Pre-Operative Exercise Intervention on Breast Cancer Proliferation and Gene Expression: Results from the Pre-Operative Health and Body (PreHAB) Study.

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Division of Women's Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
Division of Biostatistics, Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts.
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Division of Women's Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.
Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, Vermont.
Department of Surgery, Yale Comprehensive Cancer Center, New Haven, Connecticut.
University of Washington, Seattle, Washington.
Department of Surgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
Department of Oncology Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Yale School of Public Health, New Haven, Connecticut.
Contributed equally


Purpose: Exercise after breast cancer diagnosis is associated with lower cancer-specific mortality, but the biological mechanisms through which exercise impacts breast cancer are not fully understood. The Pre-Operative Health and Body (PreHAB) Study was a randomized window-of-opportunity trial designed to test the impact of exercise on Ki-67, gene expression, and other biomarkers in women with breast cancer.Experimental Design: Inactive women with newly diagnosed breast cancer were randomized to an exercise intervention or mind-body control group, and participated in the study between enrollment and surgery (mean 29.3 days). Tumor and serum were collected at baseline and surgery.Results: Forty-nine women were randomized (27 exercise, 22 control). At baseline, mean age was 52.6, body mass index was 30.2 kg/m2, and exercise was 49 minutes/week. Exercise participants significantly increased exercise versus controls (203 vs. 23 minutes/week, P < 0.0001). There were no differences in changes of expression of Ki-67, insulin receptor, and cleaved caspase-3 in exercise participants versus controls. KEGG pathway analysis demonstrated significant upregulation of 18 unique pathways between the baseline biopsy and surgical excision in exercise participants and none in control participants (q < 0.1). Top-ranked pathways included several implicated in immunity and inflammation. Exploratory analysis of tumor immune infiltrates demonstrated a trend toward a decrease in FOXP3+ cells in exercise versus control participants over the intervention period (P = 0.08).Conclusions: A window-of-opportunity exercise intervention did not impact proliferation but led to alterations in gene expression in breast tumors, suggesting that exercise may have a direct effect on breast cancer.

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