Predictive value of p27 for the benefit of adjuvant anthracycline-based chemotherapy in early breast cancer.

Abstract Abstract #6063 Background: p27 is a cyclin-dependent kinase (cdk) inhibitor that plays a role in cell cycle regulation. The expression of this protein, assessed by immunohistochemistry (IHC), has prognostic value for overall survival in breast cancer patients (Porter P.L., J Natl Cancer Inst., 2007). Based on this, we hypothesized that p27 could be a predictive factor for the efficacy of adjuvant anthracycline (A)-based chemotherapy in early breast cancer.
 Methods: Tumor samples from 823 patients, included at Institut Gustave Roussy (IGR) in two randomized trials comparing an A-based chemotherapy with no adjuvant treatment, were used to construct a tissue microarray. We previously reported predictive values of ER, Her2 expression and molecular subclassification using the same tissue array (Conforti R., Ann Oncol., 2007). Nuclear and cytoplasmic expression of p27 was assessed by the AQUA system. A p27 ratio of nuclear and cytoplasmic expression (p27 N/C ratio) was calculated for each tumor sample. The prognostic and predictive value of the continuous value of p27 N/C ratio was assessed by a Cox regression model adjusted for treatment, age, tumor grade, stage and ER expression (IHC) and stratified by trial.
 Results: p27 was assessable in 715 primary tumors. The p27 N/C ratio was significantly different according to the molecular subclasses (p=0.001) and was higher in Her2- versus Her2+ and in EGFR+ versus EGFR- tumors (p=0.0075 and p<0.0001 respectively). There was an almost significant interaction between p27 N/C ratio and disease-free survival in the adjusted Cox model (p=0.052). The adjusted hazard ratios (HR) of relapse or death of a unit increase in p27 N/C ratio was HR = 1.27 (95% CI = [0.58-2.81], p = 0.55) in the control arm and HR = 0.30 (95% CI = [0.12-0.77], p= 0.01) in the A-arm. For overall survival, the adjusted interaction p-value was equal to 0.08. The adjusted HR of death of a unit increase in p27 N/C ratio was HR=1.67 (95% CI = [0.61-1.73], p=0.32) in the control arm and HR=0.32 (95% CI = [0.10-0.99], p=0.05) in the A-arm.
 Conclusion: p27 N/C ratio, determined by the AQUA system, was borderline predictive for the efficacy of adjuvant A-based chemotherapy. However, this study is hampered by a relatively low number of events, a low dose of anthracycline, and multi-hypotheses testing (overall 20 biomarkers tested in different studies). Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6063.