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

Abstract

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 χ2 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.