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.

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.