Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients

Akt/PKB is a serine/threonine protein kinase that regulates cell cycle progression, apoptosis and growth factor mediated cell survival in association with tyrosine kinase receptors, The protein is a downstream effector of erbB-2 with implications in breast cancer progression and drug resistance in vitro. We aimed to examine the role of Akt-1 in breast cancer patients, by determining whether the expression (Akt-1) and/or activation (pAkt) were related to prognostic markers and survival. The expression of erbB-2, heregulin beta1 and Bcl-2 was also assessed by flow cytometry or immunohistochemistry, This study comprised 93 patients, aged <50 who were treated with tamoxifen and/or goserelin, We found that pAkt was associated with lower S-phase fraction (P=0.001) and the presence of heregulin betaI-expressing stromal cells (P=0.017). Neither Akt-I nor pAkt was related with other factors, Tumour cells-derived heregulin betaI was found mainly in oestrogen receptor negative (P=0.026) and node negative (P=0.005) cases. Survival analysis revealed that pAkt positive patients were more prone to relapse with distant meta-stasis, independently of S-phase fraction and nodal status (multivariate analysis; P=0.004). The results suggest that activation of Akt may have prognostic relevance in breast cancer. (C) 2002 Cancer Research UK.