title: Protein expression, survival and docetaxel benefit in node-positive breast cancer treated with adjuvant chemotherapy in the FNCLCC-PACS 01 randomized trial.
abstract: BACKGROUND
  The PACS01 trial has demonstrated that a docetaxel addition to adjuvant anthracycline-based chemotherapy improves disease-free survival (DFS) and overall survival of node-positive early breast cancer (EBC). We searched for prognostic and predictive markers for docetaxel's benefit.
  
  
  METHODS
  Tumor samples from 1,099 recruited women were analyzed for the expression of 34 selected proteins using immunohistochemistry. The prognostic and predictive values of each marker and four molecular subtypes (luminal A, luminal B, HER2-overexpressing, and triple-negative) were tested.
  
  
  RESULTS
  Progesterone receptor-negativity (HR = 0.66; 95% CI 0.47 to 0.92, P = 0.013), and Ki67-positivity (HR = 1.53; 95% CI 1.12 to 2.08, P = 0.007) were independent adverse prognostic factors. Out of the 34 proteins, only Ki67-positivity was associated with DFS improvement with docetaxel addition (adjusted HR = 0.51, 95% CI 0.33 to 0.79 for Ki67-positive versus HR = 1.10, 95% CI 0.75 to 1.61 for Ki67-negative tumors, P for interaction = 0.012). Molecular subtyping predicted the docetaxel benefit, but without providing additional information to Ki67 status. The luminal A subtype did not benefit from docetaxel (HR = 1.16, 95% CI 0.73 to 1.84); the reduction in the relapse risk was 53% (HR = 0.47, 95% CI 0.22 to 1.01), 34% (HR = 0.66, 95% CI 0.37 to 1.19), and 12% (HR = 0.88, 95% CI 0.49 to 1.57) in the luminal B, HER2-overexpressing, and triple-negative subtypes, respectively.
  
  
  CONCLUSIONS
  In patients with node-positive EBC receiving adjuvant anthracycline-based chemotherapy, the most powerful predictor of docetaxel benefit is Ki67-positivity.
authors: Department of Molecular Oncology, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, UMR891 Inserm, 232, Bd Ste-Marguerite, Marseille, 13009, France.
authors: Jocelyne
authors: J
authors: Jacquemier
authors: Jean-Marie
authors: JM
authors: Boher
authors: Henri
authors: H
authors: Roche
authors: Benjamin
authors: B
authors: Esterni
authors: Daniel
authors: D
authors: Serin
authors: Pierre
authors: P
authors: Kerbrat
authors: Fabrice
authors: F
authors: Andre
authors: Pascal
authors: P
authors: Finetti
authors: Emmanuelle
authors: E
authors: Charafe-Jauffret
authors: Anne-Laure
authors: AL
authors: Martin
authors: Mario
authors: M
authors: Campone
authors: Patrice
authors: P
authors: Viens
authors: Daniel
authors: D
authors: Birnbaum
authors: Frédérique
authors: F
authors: Penault-Llorca
authors: François
authors: F
authors: Bertucci
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D000077143:Docetaxel; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D043823:Taxoids; D000077143:Docetaxel