title: Prognostic and predictive value of p-Akt, EGFR, and p-mTOR in early breast cancer.
abstract: OBJECTIVE
  There are scarce data available on the prognostic/predictive value of p-Akt and p-mTOR protein expression in patients with high-risk early breast cancer.
  
  
  METHODS
  Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 997 patients participating in two adjuvant phase III trials were assessed for EGFR, PTEN, p-Akt, p-mTOR protein expression, and PIK3CA mutational status. These markers were evaluated for associations with each other and with selected patient and tumor characteristics, immunohistochemical subtypes, disease-free survival (DFS), and overall survival (OS).
  
  
  RESULTS
  p-mTOR protein expression was negatively associated with EGFR and positively associated with PTEN, with p-Akt473, and with the presence of PIK3CA mutations. EGFR expression was positively associated with p-Akt473, p-Akt308, and PIK3CA wild-type tumors. Finally, p-Akt308 was positively associated with p-Akt473 expression. In univariate analysis, EGFR (p = 0.016) and the coexpression of EGFR and p-mTOR (p = 0.015) were associated with poor OS. Among patients with p-Akt308-negative or low-expressing tumors, those treated with hormonal therapy were associated with decreased risk for both relapse and death (p = 0.013 and p < 0.001, respectively). In the subgroup of patients with locoregional relapse, positive EGFR and mTOR protein expression was found to be associated with increased (p = 0.034) and decreased (p < 0.001) risk for earlier relapse, respectively. In multivariate analysis, low levels of p-Akt308 and the coexpression of EGFR and p-mTOR retained their prognostic value.
  
  
  CONCLUSIONS
  Low protein expression of p-Akt308 was associated with improved DFS and OS among patients treated with hormonal therapy following adjuvant chemotherapy. Coexpression of EGFR and p-mTOR was associated with worse OS.
authors.forename: Georgios
authors.initials: G
authors.lastname: Lazaridis
authors.forename: Sofia
authors.initials: S
authors.lastname: Lambaki
authors.forename: Georgia
authors.initials: G
authors.lastname: Karayannopoulou
authors.forename: Anastasia G
authors.initials: AG
authors.lastname: Eleftheraki
authors.forename: Irene
authors.initials: I
authors.lastname: Papaspirou
authors.forename: Mattheos
authors.initials: M
authors.lastname: Bobos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Efstratiou
authors.forename: George
authors.initials: G
authors.lastname: Pentheroudakis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Zamboglou
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D055088:Early Detection of Cancer / Q000379:methods; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006115:Greece / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D011379:Prognosis; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C546842:MTOR protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases