Abstract
A subset of breast cancer patients benefits from preoperative bevacizumab and chemotherapy, but validated predictive biomarkers are lacking. Here, we aimed to evaluate tissue-based angiogenesis markers for potential predictive value regarding response to neoadjuvant bevacizumab treatment in breast cancer. In this randomized 1:1 phase II clinical trial, 132 patients with large or locally advanced HER2-negative tumors received chemotherapy ± bevacizumab. Dual Factor VIII/Ki-67 immunohistochemical staining was performed on core needle biopsies at baseline and week 12. Microvessel density (MVD), proliferative microvessel density (pMVD; Factor VIII/Ki-67 co-expression), glomeruloid microvascular proliferation (GMP), and a gene expression angiogenesis signature score, were studied in relation to pathologic complete response (pCR), clinico-pathologic features and intrinsic molecular subtype. We found that high baseline MVD (by median) significantly predicted pCR in the bevacizumab-arm (odds ratio 4.9, P = 0.012). High pMVD, presence of GMP, and the angiogenesis signature score did not predict pCR, but were associated with basal-like (P ≤ 0.009) and triple negative phenotypes (P ≤ 0.041). pMVD and GMP did also associate with high-grade tumors (P ≤ 0.048). To conclude, high baseline MVD significantly predicted response to bevacizumab treatment. In contrast, pMVD, GMP, and the angiogenesis signature score, did not predict response, but associated with aggressive tumor features, including basal-like and triple-negative phenotypes.
Highlights
A subset of breast cancer patients benefits from preoperative bevacizumab and chemotherapy, but validated predictive biomarkers are lacking
Microvessel density (MVD) and proliferative microvessel density (pMVD) were dichotomized by median values, and no significant differences were seen between the two treatment arms at baseline (Pearson’s chi-square test)
In the neoadjuvant setting, improved pathologic complete response (pCR) rates have been reported with the addition of bevacizumab to anthracycline and taxane based chemotherapy[8,9,10,11,12]
Summary
A subset of breast cancer patients benefits from preoperative bevacizumab and chemotherapy, but validated predictive biomarkers are lacking. We aimed to evaluate tissue-based angiogenesis markers for potential predictive value regarding response to neoadjuvant bevacizumab treatment in breast cancer In this randomized 1:1 phase II clinical trial, 132 patients with large or locally advanced HER2-negative tumors received chemotherapy ± bevacizumab. Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor A (VEGF-A), a key factor in this p rocess[4] It was approved by the FDA in 2 0084 for use in metastatic HER2-negative breast cancer in combination with paclitaxel[5], later studies reported only small improvements in progression-free s urvival[6,7] and no effect on overall s urvival[5,6,7]. The purpose of the study was to evaluate whether tissue-based markers of angiogenesis (MVD, pMVD, GMP, 32-gene signature) could predict response to bevacizumab treatment and provide a basis for patient stratification
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