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

Angelo Paradiso, A. Mangia, A. Chiriatti, S. Tommasi, A. Zito, A. Latorre, F. Schittulli, V. Lorusso

Research output: Contribution to journalArticle

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 χ 2). 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.

Original languageEnglish
JournalAnnals of Oncology
Volume16
Issue numberSUPPL. 4
DOIs
Publication statusPublished - May 2005

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Tubulin
Paclitaxel
Biomarkers
Breast Neoplasms
Drug Therapy
Vascular Endothelial Growth Factor Receptor-1
Tumor Biomarkers
Survival
In Situ Nick-End Labeling
Microvessels
Multivariate Analysis
Logistic Models
Regression Analysis
Neoplasms

Keywords

  • Breast cancer
  • Predictive factor
  • Taxane
  • Tubulin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Biomarkers predictive for clinical efficacy of taxol-based chemotherapy in advanced breast cancer. / Paradiso, Angelo; Mangia, A.; Chiriatti, A.; Tommasi, S.; Zito, A.; Latorre, A.; Schittulli, F.; Lorusso, V.

In: Annals of Oncology, Vol. 16, No. SUPPL. 4, 05.2005.

Research output: Contribution to journalArticle

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T1 - Biomarkers predictive for clinical efficacy of taxol-based chemotherapy in advanced breast cancer

AU - Paradiso, Angelo

AU - Mangia, A.

AU - Chiriatti, A.

AU - Tommasi, S.

AU - Zito, A.

AU - Latorre, A.

AU - Schittulli, F.

AU - Lorusso, V.

PY - 2005/5

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N2 - 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 χ 2). 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.

AB - 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 χ 2). 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.

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KW - Predictive factor

KW - Taxane

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