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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.

Author information

1
Division of Women's Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts. Jennifer_ligibel@dfci.harvard.edu.
2
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
3
Division of Biostatistics, Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts.
4
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
5
Division of Women's Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.
6
Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
7
Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, Vermont.
8
Department of Surgery, Yale Comprehensive Cancer Center, New Haven, Connecticut.
9
University of Washington, Seattle, Washington.
10
Department of Surgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.
11
Department of Oncology Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts.
12
Yale School of Public Health, New Haven, Connecticut.
#
Contributed equally

Abstract

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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