title: Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer.
abstract: OBJECTIVE
  Vascular endothelial growth factor (VEGF) is a potent molecule that mediates tumor angiogenesis primarily through VEGF receptor 2 (VEGFR2). Bevacizumab, a recombinant humanized monoclonal antibody to VEGF, was administered to previously untreated patients to evaluate parameters of angiogenesis.
  
  
  METHODS
  Twenty-one patients with inflammatory and locally advanced breast cancer were treated with bevacizumab for cycle 1 (15 mg/kg on day 1) followed by six cycles of bevacizumab with doxorubicin (50 mg/m(2)) and docetaxel (75 mg/m(2)) every 3 weeks. After locoregional therapy, patients received eight cycles of bevacizumab alone, and hormonal therapy when indicated. Tumor biopsies and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were obtained at baseline, and after cycles 1, 4, and 7.
  
  
  RESULTS
  A median decrease of 66.7% in phosphorylated VEGFR2 (Y951) in tumor cells (P = .004) and median increase of 128.9% in tumor apoptosis (P = .0008) were seen after bevacizumab alone. These changes persisted with the addition of chemotherapy. There were no significant changes in microvessel density or VEGF-A expression. On DCE-MRI, parameters reflecting reduced angiogenesis, a median decrease of 34.4% in the inflow transfer rate constant (P = .003), 15.0% in the backflow extravascular- extracellular rate constant (P = .0007) and 14.3% in extravascular-extracellular volume fraction (P = .002) were seen after bevacizumab alone.
  
  
  CONCLUSIONS
  Bevacizumab has inhibitory effects on VEGF receptor activation and vascular permeability, and induces apoptosis in tumor cells.
authors.affiliation: Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, 8901 Wisconsin Avenue, Building 8, Rm 5101, Bethesda, MD 20889-5015, USA.
authors.forename: Suparna Bonthala
authors.initials: SB
authors.lastname: Wedam
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Low
authors.forename: Sherry X
authors.initials: SX
authors.lastname: Yang
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Chow
authors.forename: Peter
authors.initials: P
authors.lastname: Choyke
authors.forename: David
authors.initials: D
authors.lastname: Danforth
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.forename: Arlene
authors.initials: A
authors.lastname: Berman
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: David J
authors.initials: DJ
authors.lastname: Liewehr
authors.forename: Jonathan
authors.initials: J
authors.lastname: Plehn
authors.forename: Arpi
authors.initials: A
authors.lastname: Doshi
authors.forename: Dave
authors.initials: D
authors.lastname: Thomasson
authors.forename: Nicole
authors.initials: N
authors.lastname: McCarthy
authors.forename: Hartmut
authors.initials: H
authors.lastname: Koeppen
authors.forename: Mark
authors.initials: M
authors.lastname: Sherman
authors.forename: JoAnne
authors.initials: J
authors.lastname: Zujewski
authors.forename: Kevin
authors.initials: K
authors.lastname: Camphausen
authors.forename: Helen
authors.initials: H
authors.lastname: Chen
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D017209:Apoptosis; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D002199:Capillary Permeability; D005260:Female; D006801:Humans; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D014407:Tumor Cells, Cultured; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D040301:Vascular Endothelial Growth Factor Receptor-2