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Class III β-Tubulin Isotype Predicts Response in Advanced Breast Cancer Patients Randomly Treated Either with Single-Agent Doxorubicin or Docetaxel

Authors' Affiliations: ¹ Université Claude Bernard Lyon 1; ² Centre Léon Bérard, Lyon, France; ³ Jules Bordet Institute, Brussels, Belgium; ⁴ Institute for Reference Materials and Measurements, European Commission, Joint Research Centre, Geel, Belgium; ⁵ Aventis Oncology, Vitry-sur-Seine, France; and ⁶ Medical Oncology Unit, Hospital of Prato, Prato, Italy

Requests for reprints: Charles Dumontet, INSERM 590, Faculté de Médecine Rockefeller, 8 avenue Rockefeller, 69008 Lyon, France. Phone: 33-4-78-77-72-36; Fax: 33-4-78-77-70-88; E-mail: charles.dumontet{at}chu-lyon.fr.

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 - and β-tubulin, classes II to IV β-tubulin isotypes, and 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 β-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 β-tubulin isotype.