Data from Gene Expression Profile and Angiogenic Markers Correlate with Response to Neoadjuvant Bevacizumab Followed by Bevacizumab plus Chemotherapy in Breast Cancer

Abstract

<div>Abstract<p><b>Purpose:</b> To identify biomarkers and gene expression profile signatures to distinguish patients with partial response (PR) from those with stable disease (SD) and progressive disease (PD).</p><p><b>Experimental Design:</b> Twenty patients with inflammatory breast cancer and one patient with locally advanced breast cancer received one cycle of bevacizumab followed by six cycles of bevacizumab plus docetaxel-doxorubicin before surgery. Baseline angiogenic/tumor markers were examined by immunohistochemistry and gene expression profiles were measured by Agilent Whole Human Genome arrays. All were assessed for clinical response.</p><p><b>Results:</b> Fourteen patients (67%, 95% confidence interval, 43-85.4%) had PR, five had SD, and two had PD. Expression of CD31 and platelet-derived growth factor receptor-β (PDGFR-β) in the tumor vasculature by immunohistochemistry was significantly associated with response (PR versus SD/PD; CD31 median, 33.5 versus 13.2; <i>P</i> = 0.0004; PDGFR-β median, 5.9 versus 0.6; <i>P</i> = 0.01). Tumor VEGF-A showed a trend towards association with response (2.65 versus 0.25; <i>P</i> = 0.04). pVEGFR2(Y996), pVEGFR2(Y951), MVD, Ki67, apoptosis, grade, ER, HER-2/<i>neu</i>, and p53 were not associated with response. Twenty-six of 1,339 Gene Ontology (GO) classes at the gene transcriptional level were differentially expressed between patients with PR and SD/PD (<i>P</i> < 0.005). Representative significant GO classes include spindle (11 genes; <i>P</i> = 0.001), vascular endothelial growth factor receptor activity including PDGFR-β (5 genes; <i>P</i> = 0.002), and cell motility including CD31 (80 genes; <i>P</i> = 0.005).</p><p><b>Conclusions:</b> Baseline CD31, PDGFR-β, and GO classes for vascular endothelial growth factor receptor activity and mitosis were significantly associated with response to bevacizumab followed by bevacizumab plus chemotherapy.</p></div>