Clinical significance of pAkt and pErk1/2 expression in early-stage breast cancer patients treated with anthracycline-based adjuvant chemotherapy

摘要

The expression of phosphorylated Akt (pAkt) and phosphorylated extracellular-regulated kinase 1/2 (pErk1/2) proteins may result in breast cancer progression and drug resistance in vitro, however, compelling evidence regarding the clinical significance of pAkt and pErk1/2 in early-stage breast cancer is currently lacking. Thus, the aim of the present study was to determine the prognostic value of pAkt and pErk1/2 expression in early-stage breast cancer patients treated with anthracycline-based adjuvant chemotherapy. Tumor specimens were obtained from 256 patients with early-stage breast cancer who had been treated with anthracycline-based adjuvant chemotherapy, and pAkt and pErk1/2 protein expression was immunohistochemically determined. The interactions between pAkt, pErk1/2 and clinical characteristics were assessed by performing (2) tests, and survival functions were estimated using the Kaplan-Meier method. It was identified that pAkt and pErk1/2 were expressed in 38.7 and 33.6% of patients, respectively, and that pAkt protein expression was correlated with pErk1/2 protein expression (P<0.001). In addition, after a median follow-up period of 52.5 months, the patients with pAkt- and pErk1/2-negative tumors experienced a significantly longer disease-free survival (DFS) time compared with pAkt- or pErk1/2-positive patients (P=0.028). pErk1/2 expression was associated with the decreased DFS time of the patients (P=0.049), and pAkt and pErk1/2 expression were associated with the decreased DFS time in human epidermal growth factor receptor (HER2)-positive patients (P=0.002). pErk1/2 expression was associated with chemotherapy resistance (P=0.016). Thus, the coexpression of pAkt and pErk1/2 was an independent factor for a poor prognosis in early-stage and HER2-positive breast cancer patients. By contrast, pErk1/2 expression alone may be a poor predictor for determining the efficacy of anthracycline-based chemotherapy.