Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer

Suparna Bonthala Wedam, Jennifer A. Low, Sherry X. Yang, Catherine K. Chow, Peter Choyke, David Danforth, Stephen M. Hewitt, Arlene Berman, Seth M. Steinberg, David J. Liewehr, Jonathan Plehn, Arpi Doshi, Dave Thomasson, Nicole McCarthy, Hartmut Koeppen, Mark Sherman, Jo Anne Zujewski, Kevin Camphausen, Helen Chen, Sandra M. Swain

Research output: Contribution to journalArticle

451 Scopus citations

Abstract

Purpose: 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. Patients and 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/m2) and docetaxel (75 mg/m2) 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. Conclusion: Bevacizumab has inhibitory effects on VEGF receptor activation and vascular permeability, and induces apoptosis in tumor cells.

Original languageEnglish (US)
Pages (from-to)769-777
Number of pages9
JournalJournal of Clinical Oncology
Volume24
Issue number5
DOIs
StatePublished - Feb 10 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wedam, S. B., Low, J. A., Yang, S. X., Chow, C. K., Choyke, P., Danforth, D., Hewitt, S. M., Berman, A., Steinberg, S. M., Liewehr, D. J., Plehn, J., Doshi, A., Thomasson, D., McCarthy, N., Koeppen, H., Sherman, M., Zujewski, J. A., Camphausen, K., Chen, H., & Swain, S. M. (2006). Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. Journal of Clinical Oncology, 24(5), 769-777. https://doi.org/10.1200/JCO.2005.03.4645