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


METHODS
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.
Galmarini
Carlos M
CM
Université Claude Bernard Lyon 1, France.
Treilleux
Isabelle
I
Cardoso
Fatima
F
Bernard-Marty
Chantal
C
Durbecq
Virginie
V
Gancberg
David
D
Bissery
Marie-Christine
MC
Paesmans
Marianne
M
Larsimont
Denis
D
Piccart
Martine J
MJ
Di Leo
Angelo
A
Dumontet
Charles
C
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D000077143:Docetaxel; D004317:Doxorubicin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020033:Protein Isoforms / Q000096:biosynthesis; D043823:Taxoids / Q000627:therapeutic use*; D014404:Tubulin / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D020033:Protein Isoforms; D043823:Taxoids; D014404:Tubulin; D000077143:Docetaxel; D004317:Doxorubicin