Assessing early therapeutic response to bevacizumab in primary breast cancer using magnetic resonance imaging and gene expression profiles

J Natl Cancer Inst Monogr. 2011;2011(43):71-4. doi: 10.1093/jncimonographs/lgr027.

Abstract

Antiangiogenic therapy is a promising approach for the treatment of breast cancer. In practice, however, only a subset of patients who receive antiangiogenic drugs demonstrate a significant response. A key challenge, therefore, is to discover biomarkers that are predictive of response to antiangiogenic therapy. To address this issue, we have designed a window-of-opportunity study in which bevacizumab is administered as a short-term first-line treatment to primary breast cancer patients. Central to our approach is the use of a detailed pharmacodynamic assessment, consisting of pre- and post-bevacizumab multi-parametric magnetic resonance imaging scans and core biopsies for exon array gene expression analysis. Here, we illustrate three intrinsic patterns of response to bevacizumab and discuss the molecular mechanisms that may underpin each. Our results illustrate how the combination of dynamic imaging data and gene expression profiles can guide the development of biomarkers for predicting response to antiangiogenic therapy.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab
  • Biomarkers, Tumor / metabolism*
  • Biopsy, Needle / methods
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Chemotherapy, Adjuvant
  • Contrast Media
  • Female
  • Gadolinium DTPA
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Magnetic Resonance Imaging* / methods
  • Neoadjuvant Therapy
  • Predictive Value of Tests
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Contrast Media
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Receptors, Vascular Endothelial Growth Factor
  • Gadolinium DTPA