Circulating biomarkers of bevacizumab activity in patients with breast cancer

Cancer Biol Ther. 2008 Jan;7(1):15-20. doi: 10.4161/cbt.7.1.5337. Epub 2007 Nov 21.


Purpose: Noninvasive markers of anti-vascular endothelial growth factor (VEGF) therapy are needed. Soluble vascular cell adhesion molecule (sVCAM-1), soluble VEGF receptor-2 (sVEGFR-2), and plasma VEGF levels were assessed as potential biomarkers of therapy with bevacizumab. Tumor samples were evaluated for VEGFR-2 mutations before and after bevacizumab.

Experimental design: Twenty-one patients with breast cancer underwent neoadjuvant treatment with bevacizumab for 1 cycle followed by 6 cycles of bevacizumab, chemotherapy, and filgrastim. Peripheral blood samples were collected at baseline, post cycles 1, 4 and 7. sVCAM-1, VEGF and sVEGFR-2 levels were measured by enzyme-linked immunosorbent assay (ELISA). Exons 17-26 of VEGFR-2 were sequenced on tissue samples from 20 patients at baseline and post cycle 1 to evaluate for tumor mutations.

Results: From baseline to post cycle 1, sVCAM-1 and sVEGFR-2 values increased by a median of 180.5 ng/ml (p < 0.0001) and 1927 ng/ml respectively (p = 0.0003). Baseline VEGF, sVEGFR-2, and sVCAM-1 levels nor changes in sVEGFR-2 and sVCAM-1 levels were associated with clinical response. Median baseline sVEGFR-2 levels were 11322 ng/ml and 7524 ng/ml in patients with (n = 5) and without (n = 6) wound healing problems respectively, (p = 0.052). In 40 samples where tumor VEGFR-2 sequencing was obtained, no mutations were seen compared to the reference sequence.

Conclusions: sVCAM-1 and sVEGFR-2 values increased significantly after treatment with bevacizumab, possibly due to compensatory mechanisms secondary to VEGF inhibition. sVEGFR-2 levels were somewhat higher in patients with wound healing problems and may potentially predict patients at higher risk of this complication. There were no tumor VEGFR-2 mutations.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Middle Aged
  • Mutation
  • Vascular Cell Adhesion Molecule-1 / blood*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor Receptor-2 / blood*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Vascular Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Vascular Endothelial Growth Factor Receptor-2