p53, HER2 and tumor cell apoptosis correlate with clinical outcome after neoadjuvant bevacizumab plus chemotherapy in breast cancer

Bevacizumab, an antibody to vascular endothelial growth factor (VEGF), has been incorporated into chemotherapy regimens in the treatment of several cancer types including breast cancer. The aim of this study was to identify tumor and angiogenic factors that potentially associate with outcome. In a pilot trial, 21 patients with inflammatory breast cancer and locally advanced breast cancer received bevacizumab plus doxorubicin-docetaxel chemotherapy before surgery. Baseline p53, HER2, tumor apoptosis, Ki67, estrogen receptor (ER), VEGF-A, serum VEGF (sVEGF), VEGFR2-Y951 and microvessel density (MVD) were prospectively designed and determined by immunohistochemistry and enzyme-linked immunosorbent assay. Hazard ratios (HR) and 95% confidence intervals for survival and progression-free survival (PFS) were estimated using Cox proportional hazards analyses. With a median follow-up of 65.9 months, patients with low apoptosis or p53-negative tumors had significantly longer survival than those with high apoptosis or p53-positive tumors (median 61.5 vs. 20.2 months; HR 0.22; p=0.011 for apoptosis and median 59.6 vs. 24.2 months; HR 0.27; p=0.016 for p53). Low Ki67 versus high Ki67 exhibited a trend towards association with survival (median 57.1 vs. 17.3 months, HR 0.34, p=0.07). Patients with HER2-negative tumors had significantly longer PFS than those with HER2-positive tumors (median 31.2 vs. 9.4 months; HR 0.23; p=0.03). ER, VEGF-A, sVEGF, VEGFR2-Y951 and MVD were not significantly associated with outcome. Our data suggest that baseline p53, apoptosis and HER2 are each significantly associated with outcome in patients who received bevacizumab plus chemotherapy.