Class III beta-tubulin isotype predicts response in advanced breast cancer patients randomly treated either with single-agent doxorubicin or docetaxel

Clin Cancer Res. 2008 Jul 15;14(14):4511-6. doi: 10.1158/1078-0432.CCR-07-4741.

Abstract

Purpose: To evaluate the role of microtubule-associated variables as potential predictors of response and clinical outcome in patients with advanced breast cancer receiving single-agent docetaxel or doxorubicin chemotherapy.

Experimental design: The analysis was done on 173 tumor samples from patients with locally advanced or metastatic breast cancer who have participated in the TAX-303 phase III trial in which patients were randomly assigned to receive docetaxel or doxorubicin. Expression of total alpha- and beta-tubulin, classes II to IV beta-tubulin isotypes, and tau protein was evaluated by immunohistochemistry on formalin-fixed, paraffin-embedded tumors from the primary breast cancer.

Results: We observed that patients with "high" expression of class III beta-tubulin isotype had a higher probability of response to docetaxel than to doxorubicin treatment (odds ratio, 1.9; 95% confidence interval, 1.01-3.7; P = 0.05). No difference was observed in terms of time to progression or in terms of overall survival.

Conclusions: This study suggests that the superiority of docetaxel over doxorubicin seems to be confined to the subgroup of patients with "high" expression of class III beta-tubulin isotype.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Docetaxel
  • Doxorubicin / therapeutic use*
  • Drug Resistance, Neoplasm / physiology
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Protein Isoforms / biosynthesis
  • Taxoids / therapeutic use*
  • Tubulin / biosynthesis*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Isoforms
  • Taxoids
  • Tubulin
  • Docetaxel
  • Doxorubicin