Biomarkers predictive for clinical efficacy of taxol-based chemotherapy in advanced breast cancer

Abstract

Background: Several studies looked for tumor biomarkers predictive for paclitaxel sensitivity but till now no reliable biomarkers are available. The aim of this study was to verify the potential predictive value of β-tubulin III and IV, vascular endothelial growth factor-receptor (VEGFR-1), HER2/neu and microvessel density (mVD), in a group of 70 patients with advanced breast cancer (ABC) treated with paclitaxel-based chemotherapy. Patients and methods: Immunohistochemical analysis (ICA) of HER2, VEGFR-1, mVd, β-tubulin III and β-tubulin IV expression were performed in a series of 72 advanced breast cancer. Furthermore apoptotic fraction with TUNEL analysis was evaluated. Results: β-tubulin III ICA expression was predictive of progression after chemotherapy. In fact only 2% of the patients with low β-tubulin III expression progressed after paclitaxel chemotherapy vs 38% of those with high β-tubulin III tumor expression (P=0.000; by χ2). This evidence was confirmed by a logistic regression analysis (OR 28.789; 95% CI 3.212-258,072; P=0.004). There was not a significant association between other biomarkers' characteristics and clinical response to chemotherapy. A Cox multivariate analysis, with overall survival as a dependent variable, showed that only HER2 expression was independently associated (OR 2.39; 95% CI 1.09-5.23; P=0.03) with overall survival. Conclusions: We suggest that class III β-tubulin immunohistochemical expression analysis could be a potentially relevant tumor biomarker for paclitaxel resistance in advanced breast cancer patients. © 2005 European Society for Medical Oncology.