title: Modulation of circulating angiogenic factors and tumor biology by aerobic training in breast cancer patients receiving neoadjuvant chemotherapy.
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 ((15)O-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). (15)O-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.
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Box 3085, Durham, NC 27710, USA. lee.w.jones@duke.edu
authors.forename: Lee W
authors.initials: LW
authors.lastname: Jones
authors.forename: Diane R
authors.initials: DR
authors.lastname: Fels
authors.forename: Miranda
authors.initials: M
authors.lastname: West
authors.forename: Jason D
authors.initials: JD
authors.lastname: Allen
authors.forename: Gloria
authors.initials: G
authors.lastname: Broadwater
authors.forename: William T
authors.initials: WT
authors.lastname: Barry
authors.forename: Lee G
authors.initials: LG
authors.lastname: Wilke
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Masko
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Douglas
authors.forename: Rajesh C
authors.initials: RC
authors.lastname: Dash
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Povsic
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Peppercorn
authors.forename: P Kelly
authors.initials: PK
authors.lastname: Marcom
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Blackwell
authors.forename: Gretchen
authors.initials: G
authors.lastname: Kimmick
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Turkington
authors.forename: Mark W
authors.initials: MW
authors.lastname: Dewhirst
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005081:Exercise Therapy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D004317:Doxorubicin; D003520:Cyclophosphamide