期刊
CANCER PREVENTION RESEARCH
卷 6, 期 9, 页码 925-937出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1940-6207.CAPR-12-0416
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- United States Department of Defense Breast Cancer Research Program of the Office of the Congressionally Directed Medical Research Programs-Ideas Award
- NIH [CA40355]
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 (O-15-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 x 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 x group interactions in CEPs and select CAFs [placenta growth factor, interleukin (IL)-1 beta, and IL-2], also favoring the AC+AET group (P < 0.05). O-15-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-kappa B. 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. (C)2013 AACR.
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