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


METHODS
Immunohistochemical analysis (ICA) of HER2, VEGFR-1, mVd, beta-tubulin III and beta-tubulin IV expression were performed in a series of 72 advanced breast cancer. Furthermore apoptotic fraction with TUNEL analysis was evaluated.


RESULTS
beta-tubulin III ICA expression was predictive of progression after chemotherapy. In fact only 2% of the patients with low beta-tubulin III expression progressed after paclitaxel chemotherapy vs 38% of those with high beta-tubulin III tumor expression (P=0.000; by chi(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 beta-tubulin immunohistochemical expression analysis could be a potentially relevant tumor biomarker for paclitaxel resistance in advanced breast cancer patients.
Paradiso
A
A
Clinical Experimental Oncology Laboratory, National Cancer Institute, via Amendola 209, 70125 Bari, Italy. a.paradiso@oncologico.bari.it
Mangia
A
A
Chiriatti
A
A
Tommasi
S
S
Zito
A
A
Latorre
A
A
Schittulli
F
F
Lorusso
V
V
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy*; D002462:Cell Membrane / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D004727:Endothelium / Q000737:chemistry; D015251:Epirubicin / Q000008:administration & dosage; D004848:Epithelium / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D016896:Treatment Outcome; D014404:Tubulin / Q000032:analysis*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis*
D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D015251:Epirubicin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D014404:Tubulin; D040281:Vascular Endothelial Growth Factor Receptor-1