VEGF Gene Amplification/Deletion and Haplotype as Biomarkers for Bevacizumab in Breast Cancer

OBJECTIVES:

Primary

• To demonstrate that vascular endothelial growth factor-A (VEGFA) haplotypes that are associated with an increased VEGFA expression will predict superior outcome for patients with metastatic breast cancer receiving bevacizumab in ECOG-E2100 (but not for the control arm).
• To demonstrate that candidate single nucleotide polymorphisms (SNPs) will further improve the predictive capacity of outcome (efficacy and toxicity) in patients enrolled in ECOG-E2100.
• To demonstrate that tumor VEGFA amplification or borderline amplification (estimated 14% frequency) will predict superior outcome for patients with metastatic breast cancer receiving bevacizumab on ECOG-E2100 whereas those with VEGFA deletion (estimated 11% frequency) will predict inferior outcome.
• To demonstrate that VEGFA amplification/deletion will not predict outcome in the control arm of ECOG-E2100.

Secondary

• To demonstrate that tumor VEGFA amplification will predict increased protein expression as ascertained by IHC.
• To demonstrate that a combined algorithm calculated from tumor-specific variability (VEGFA amplification/deletion) and host-specific variability (SNPs) will optimally predict outcome (efficacy) with bevacizumab in patients enrolled on ECOG-E2100.