title: Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer.
abstract: Taxanes and anthracyclines improve the outcome of early breast cancer, although the benefit is limited to a small proportion of patients and are toxic. We prospectively looked for predictors of response to these drugs.
  
  
  METHODS
  Four cycles of doxorubicin (75 mg/m²) or docetaxel (100 mg/m²) were compared as presurgical chemotherapy for breast cancer. Biomarkers were determined by immunohistochemistry and fluorescent in situ hybridization using prechemotherapy core biopsies. Tumors were also classified into one of the molecular intrinsic subtypes using an immunohistochemical panel of five biomarkers and genomic profiles. Single genes and intrinsic subtypes were correlated with response to doxorubicin versus docetaxel. Among the 204 evaluable patients, significant predictors of sensitivity in multivariate analysis were low topo2a expression and ER-negative status for doxorubicin and small tumor size and ER-negative status for docetaxel. Predictors of resistance in multivariate analysis were triple-negative status (ER/PgR/HER2 negative by IHC/FISH) for doxorubicin, and high TNM stage for docetaxel. Triple-negative tumors were associated with topo2a overexpression more than the other subtypes. In 94 patients with gene expression profiles, docetaxel was superior to doxorubicin in the basal-like subtype (good pathological response rate - PCR + class I of 56 vs. 0%; P = 0.034); no significant differences were observed in the other subtypes when comparing these two drugs. Low topo2a expression and ER-negative status were predictors of response to doxorubicin, while small tumor size and ER-negative status predicted response to docetaxel. Docetaxel was superior to doxorubicin in triple-negative/basal-like tumors, while no significant differences were seen in the remaining intrinsic subtypes.
authors.affiliation: Servicio de Oncología Médica, Hospital Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain. miguel.martin@salud.madrid.org
authors.forename: M
authors.initials: M
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: Romero
authors.forename: M C U
authors.initials: MC
authors.lastname: Cheang
authors.forename: J A
authors.initials: JA
authors.lastname: López García-Asenjo
authors.forename: J A
authors.initials: JA
authors.lastname: García-Saenz
authors.forename: B
authors.initials: B
authors.lastname: Oliva
authors.forename: J M
authors.initials: JM
authors.lastname: Román
authors.forename: X
authors.initials: X
authors.lastname: He
authors.forename: A
authors.initials: A
authors.lastname: Casado
authors.forename: J
authors.initials: J
authors.lastname: de la Torre
authors.forename: V
authors.initials: V
authors.lastname: Furio
authors.forename: J
authors.initials: J
authors.lastname: Puente
authors.forename: T
authors.initials: T
authors.lastname: Caldés
authors.forename: J A
authors.initials: JA
authors.lastname: Vidart
authors.forename: Sara
authors.initials: S
authors.lastname: Lopez-Tarruella
authors.forename: E
authors.initials: E
authors.lastname: Diaz-Rubio
authors.forename: C M
authors.initials: CM
authors.lastname: Perou
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000235:genetics*; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000235:genetics*; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000077143:Docetaxel; D004317:Doxorubicin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D004250:DNA Topoisomerases, Type II