Modulation of Circulating Angiogenic Factors and Tumor Biology by Aerobic Training in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
- 1 September 2013
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Prevention Research
- Vol. 6 (9), 925-937
- https://doi.org/10.1158/1940-6207.capr-12-0416
Abstract
Aerobic exercise training (AET) is an effective adjunct therapy to attenuate the adverse side-effects of adjuvant chemotherapy in women with early breast cancer. Whether AET interacts with the antitumor efficacy of chemotherapy has received scant attention. We carried out a pilot study to explore the effects of AET in combination with neoadjuvant doxorubicin–cyclophosphamide (AC+AET), relative to AC alone, on: (i) host physiology [exercise capacity (VO2 peak), brachial artery flow-mediated dilation (BA-FMD)], (ii) host-related circulating factors [circulating endothelial progenitor cells (CEP) cytokines and angiogenic factors (CAF)], and (iii) tumor phenotype [tumor blood flow (15O–water PET), tissue markers (hypoxia and proliferation), and gene expression] in 20 women with operable breast cancer. AET consisted of three supervised cycle ergometry sessions/week at 60% to 100% of VO2 peak, 30 to 45 min/session, for 12 weeks. There was significant time × group interactions for VO2 peak and BA-FMD, favoring the AC+AET group (P < 0.001 and P = 0.07, respectively). These changes were accompanied by significant time × group interactions in CEPs and select CAFs [placenta growth factor, interleukin (IL)-1β, and IL-2], also favoring the AC+AET group (P < 0.05). 15O–water positron emission tomography (PET) imaging revealed a 38% decrease in tumor blood flow in the AC+AET group. There were no differences in any tumor tissue markers (P > 0.05). Whole-genome microarray tumor analysis revealed significant differential modulation of 57 pathways (P < 0.01), including many that converge on NF-κB. Data from this exploratory study provide initial evidence that AET can modulate several host- and tumor-related pathways during standard chemotherapy. The biologic and clinical implications remain to be determined. Cancer Prev Res; 6(9); 925–37. ©2013 AACR.Keywords
This publication has 87 references indexed in Scilit:
- Exercise interventions on health-related quality of life for people with cancer during active treatmentCochrane Database of Systematic Reviews, 2012
- Exercise interventions on health-related quality of life for cancer survivorsCochrane Database of Systematic Reviews, 2012
- Exercise training inhibits inflammatory cytokines and more than prevents myocardial dysfunction in rats with sustained β‐adrenergic hyperactivityThe Journal of Physiology, 2010
- Effect of aerobic exercise on tumor physiology in an animal model of human breast cancerJournal of Applied Physiology, 2010
- Exercise protects the cardiovascular system: effects beyond traditional risk factorsThe Journal of Physiology, 2009
- Australian Association for Exercise and Sport Science position stand: Optimising cancer outcomes through exerciseJournal of Science and Medicine in Sport, 2009
- Antiangiogenic Therapy Elicits Malignant Progression of Tumors to Increased Local Invasion and Distant MetastasisCancer Cell, 2009
- Common endothelial progenitor cell assays identify discrete endothelial progenitor cell populationsAmerican Heart Journal, 2009
- Rapid Chemotherapy-Induced Acute Endothelial Progenitor Cell Mobilization: Implications for Antiangiogenic Drugs as Chemosensitizing AgentsCancer Cell, 2008
- Tumour maintenance is mediated by eNOSNature, 2008