Activation of angiogenic pathway in the prediction of pathologic response to bevacizumab-based neoadjuvant therapy in breast cancer.

Abstract

10595 Background: To evaluate potential biomarkers of pathological response to bevacizumab-based neoadjuvant therapy in untreated breast cancers (BC) patients recruited in a phase II, multicenter clinical trial. Methods: Patients received a single infusion of bevacizumab (15 mg/ kg) (C1) 3 weeks prior to the beginning of neoadjuvant chemotherapy (NAC) consisting in 4 cycles of docetaxel (60 mg/mq), doxorubicin (50 mg/mq) and bevacizumab (15 mg/ kg) every 21 days (C2-C5) following by surgery. Biomarker expression was assessed by immunohistochemistry (Ki67, CD31, CD31/Ki67, VEGFR2, pVEGFR2 [Y951]) before and after bevacizumab infusion (C1). Gene expression was analyzed using Affimetrix Human Gene ST 1.0. Results: This analysis was performed on 73 patients (49 yr, range 29-70). Twenty (27%) patients obtained best response (G4-G5) whether 50 (68%) were considered as no responder (G1-G2-G3). Response was associated with negative estrogen receptors expression (p=0.02) and high Ki67 basal and after C1 expression (p=0.009 and p=0.01). Six (54%) of the triple negative tumors were responders (p=0.05). Interestingly, change in pVEGFR2 [Y951] staining induced by bevacizumab administration was found significantly associated with response (p=0.0). Decrease in the phosphorilation status of VEGFR2 (Y951) >70% yielded a receiver operating characteristic (ROC) curve area of 0.681 (95% CI: 0.536 - 0.825) with 84% sensitivity and 95% specificity. The positive and negative predictive values for this marker were 60% and 64%, respectively. The change in phosphorilation status of VEGFR2p remains a significant predictor biomarker of response in multivariate analysis (OR=0.9, IC%95 0.96-0.99, p=0.04) after adjusting for clinical-pathological characteristics. Conclusions: These findings suggest the role of the phosphorilation status of VEGFR2 as predictive biomarkers of pathological response to bevacizumab in neoadjuvant setting in breast cancer.