title: Microtubule-associated parameters as predictive markers of docetaxel activity in advanced breast cancer patients: results of a pilot study.
abstract: Docetaxel is currently one of the most active agents for breast cancer. Predictive markers of docetaxel efficacy are clearly needed in order to avoid unnecessary toxicity in nonresponding or resistant patients and to improve the cost-effectiveness ratio of docetaxel. This pilot study correlates the clinical efficacy of docetaxel in 54 metastatic or locally advanced breast cancer patients with the expression of microtubule-associated parameters evaluated by immunohistochemistry in archival tumor samples. Among the 41 eligible patients (evaluable response to docetaxel and available predocetaxel treatment paraffin-embedded tumor tissue), response to docetaxel was: partial response 54%, stable disease 29%, and progressive disease 17%. Alfa- and b-tubulin and Tau protein were expressed in the majority of tumor samples. Class II, III, and IV b-tubulin isotypes were expressed in 56%, 65%, and 82% of samples, respectively. No clear association was found between response to docetaxel and the level of expression of Tau protein, a- and b-tubulin, and class III and IV b-tubulin isotypes. In patients with class II b-tubulin-positive tumors, the response rate was 39%, while in class II b-tubulin-negative tumors the response rate was 79% (P = 0.04). Therefore, we conclude that the class II b-tubulin isotype seems to be a promising predictive marker of docetaxel activity. Nevertheless, further investigations are needed due to the limited number of patients evaluated in this pilot study.
authors.affiliation: Translational Research Unit, Jules Bordet Institute, Brussels, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Bernard-Marty
authors.forename: Isabelle
authors.initials: I
authors.lastname: Treilleux
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
authors.forename: Fatima
authors.initials: F
authors.lastname: Cardoso
authors.forename: Arlette
authors.initials: A
authors.lastname: Fellous
authors.forename: David
authors.initials: D
authors.lastname: Gancberg
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Bissery
authors.forename: Marianne
authors.initials: M
authors.lastname: Paesmans
authors.forename: Denis
authors.initials: D
authors.lastname: Larsimont
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Piccart
authors.forename: Angelo
authors.initials: A
authors.lastname: Di Leo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D001859:Bone Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008870:Microtubules; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011379:Prognosis; D012680:Sensitivity and Specificity; D012983:Soft Tissue Neoplasms / Q000556:secondary; D016019:Survival Analysis; D043823:Taxoids; D016896:Treatment Outcome; D014404:Tubulin / Q000032:analysis*; D016875:tau Proteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D043823:Taxoids; D014404:Tubulin; D016875:tau Proteins; D000077143:Docetaxel; D017239:Paclitaxel