Evaluation of the prognostic value of p53 and Bcl-2 in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy (DSAC)

Abstract

627 Background: To assess the prognostic significance of positive p53 and Bcl-2 expression in high-risk patients with breast cancer treated with DSAC. Methods: From 11–6-1997 until 2–11-2000, 595 eligible patients were randomized to receive DSAC with epirubicin and intensified CMF with or without paclitaxel. In 397 patients, p53 and Bcl-2 were assessed centrally by immunohistochemistry (IHC) using NeXes automated system (Ventana). Both P53 and Bcl-2 data were available in 375 patients. Results: p53 and Bcl-2 expression was detected in 100 (25.5%) and 194 (49%) patients, respectively. The absence of Bcl-2 expression was significantly higher in patients with p53 expression (p=0.04). Incidence of p53 immuno-positivity was significantly higher in patients with grade III tumors (p<0.001) or negative hormonal receptor (HR) status (p<0.001). The rate of disease progression and death was significantly higher among patients with p53 expression (p=0.004 and p=0.006 respectively). Additionally, negative HR status, was more often recorded among patients with absence of Bcl-2 expression (p=0.002). After adjustment was made for treatment group, patients with absence of Bcl-2 expression and p53 expression had a significantly increased risk of both disease recurrence and death. Conclusions:p53 immuno-positivity was significantly associated with poor prognostic factors and higher incidence of disease relapse and death in patients with breast cancer treated with dose-dense sequential adjuvant chemotherapy. Absence of Bcl-2 expression was related only with negative HR status. No significant financial relationships to disclose.