title: Association between the nuclear to cytoplasmic ratio of p27 and the efficacy of adjuvant polychemotherapy in early breast cancer.
abstract: BACKGROUND
  The purpose of this study was to evaluate the prognostic and predictive value of p27 expression in patients with early breast cancer.
  
  
  METHODS
  Quantitative immunofluorescence assays for p27 were done on a tissue microarray that included 823 samples from patients randomized between anthracycline-based chemotherapy and no chemotherapy. Quantification of p27 was done using the AQUA® system (HistoRx, Inc., Branford, CT). Both p27 nuclear expression and the nuclear to cytoplasmic ratio were assessed.
  
  
  RESULTS
  Nuclear p27 expression was not predictive for the efficacy of anthracycline-based chemotherapy [adjusted P=0.18 for disease-free survival (DFS)] nor prognostic [95% confidence interval (CI) 0.99-1.01, P=0.49]. However, p27 nuclear/cytoplasmic ratio was predictive for the efficacy of adjuvant chemotherapy (adjusted P=0.016 DFS). The adjusted hazard ratio (HR) for relapse associated with adjuvant chemotherapy was 0.56 (95% CI 0.37-0.84, P=0.005) and 1.06 (95% CI 0.76-1.47, P=0.74) for patients with high and low nuclear/cytoplasmic ratio, respectively. p27 N/C ratio was prognostic in patients treated with chemotherapy (HR for relapse or death for a 1 unit increase in p27 N/C ratio was 0.30, 95% CI 0.12-0.77) but not in the untreated arm (HR for relapse or death was 1.27, 95% CI 0.58-2.8).
  
  
  CONCLUSIONS
  This study did not confirm the role of p27 nuclear expression as a prognostic parameter. However, the p27 nuclear/cytoplasmic ratio was predictive in patients treated with anthracycline-based chemotherapy.
authors.affiliation: Department of Medical Oncology, Institute Gustave Roussy, Villejuif; INSERM Unit U981; Biomarkers and New Therapeutic Targets, Université Paris Sud, Institut Gustave Roussy, Villejuif, France. Electronic address: fandre@igr.fr.
authors.forename: F
authors.initials: F
authors.lastname: Andre
authors.affiliation: Department of Medical Oncology, Institute Gustave Roussy, Villejuif.
authors.forename: R
authors.initials: R
authors.lastname: Conforti
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, USA.
authors.forename: C B
authors.initials: CB
authors.lastname: Moeder
authors.affiliation: Unit of Biostatistics and Epidemiology.
authors.forename: A
authors.initials: A
authors.lastname: Mauguen
authors.affiliation: Department of Medical Oncology, Institute Gustave Roussy, Villejuif.
authors.forename: M
authors.initials: M
authors.lastname: Arnedos
authors.affiliation: Department of Medical Oncology, Institute Gustave Roussy, Villejuif.
authors.forename: N
authors.initials: N
authors.lastname: Berrada
authors.affiliation: Department of Medical Oncology, Institute Gustave Roussy, Villejuif.
authors.forename: S
authors.initials: S
authors.lastname: Delaloge
authors.affiliation: Department of Pathology, Institut Gustave Roussy, Villejuif, France.
authors.forename: G
authors.initials: G
authors.lastname: Tomasic
authors.affiliation: Department of Medical Oncology, Institute Gustave Roussy, Villejuif.
authors.forename: M
authors.initials: M
authors.lastname: Spielmann
authors.affiliation: Department of Breast Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Esteva
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Rimm
authors.affiliation: Unit of Biostatistics and Epidemiology; Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Bruxelles, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Michiels
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003593:Cytoplasm / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D055815:Young Adult
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil