Association between the nuclear to cytoplasmic ratio of p27 and the efficacy of adjuvant polychemotherapy in early breast cancer

Ann Oncol. 2012 Aug;23(8):2059-2064. doi: 10.1093/annonc/mdr569. Epub 2012 Jan 11.

Abstract

Background: The purpose of this study was to evaluate the prognostic and predictive value of p27 expression in patients with early breast cancer.

Patients and 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Cell Nucleus / metabolism
  • Chemotherapy, Adjuvant
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Cyclophosphamide / administration & dosage
  • Cytoplasm / metabolism
  • Doxorubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Young Adult

Substances

  • Cyclin-Dependent Kinase Inhibitor p27
  • Doxorubicin
  • Cyclophosphamide
  • Fluorouracil