Gene expression profile and angiogenic marker correlates with response to neoadjuvant bevacizumab followed by bevacizumab plus chemotherapy in breast cancer.
OBJECTIVE
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).


METHODS
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.


RESULTS
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-beta (PDGFR-beta) in the tumor vasculature by immunohistochemistry was significantly associated with response (PR versus SD/PD; CD31 median, 33.5 versus 13.2; P = 0.0004; PDGFR-beta median, 5.9 versus 0.6; P = 0.01). Tumor VEGF-A showed a trend towards association with response (2.65 versus 0.25; P = 0.04). pVEGFR2(Y996), pVEGFR2(Y951), MVD, Ki67, apoptosis, grade, ER, HER-2/neu, 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 (P < 0.005). Representative significant GO classes include spindle (11 genes; P = 0.001), vascular endothelial growth factor receptor activity including PDGFR-beta (5 genes; P = 0.002), and cell motility including CD31 (80 genes; P = 0.005).


CONCLUSIONS
Baseline CD31, PDGFR-beta, and GO classes for vascular endothelial growth factor receptor activity and mitosis were significantly associated with response to bevacizumab followed by bevacizumab plus chemotherapy.
Yang
Sherry X
SX
National Clinical Target Validation Laboratory, Division of Cancer Treatment and Diagnosis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA. xy32m@nih.gov
Steinberg
Seth M
SM
Nguyen
Dat
D
Wu
Thomas D
TD
Modrusan
Zora
Z
Swain
Sandra M
SM
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D020869:Gene Expression Profiling; D006801:Humans; D020360:Neoadjuvant Therapy; D015398:Signal Transduction; D043823:Taxoids / Q000008:administration & dosage; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077143:Docetaxel; D000068258:Bevacizumab; D004317:Doxorubicin
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