BACKGROUND AND PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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.
BACKGROUND AND PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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: José Baselga; Mario Campone; Martine Piccart; Howard A Burris; Hope S Rugo; Tarek Sahmoud; Shinzaburo Noguchi; Michael Gnant; Kathleen I Pritchard; Fabienne Lebrun; J Thaddeus Beck; Yoshinori Ito; Denise Yardley; Ines Deleu; Alejandra Perez; Thomas Bachelot; Luc Vittori; Zhiying Xu; Pabak Mukhopadhyay; David Lebwohl; Gabriel N Hortobagyi Journal: N Engl J Med Date: 2011-12-07 Impact factor: 91.245
Authors: D Dionysopoulos; K Pavlakis; V Kotoula; E Fountzilas; K Markou; I Karasmanis; N Angouridakis; A Nikolaou; K T Kalogeras; G Fountzilas Journal: Strahlenther Onkol Date: 2013-02-13 Impact factor: 3.621
Authors: Rulla M Tamimi; A Heather Eliassen; Tengteng Wang; Yujing J Heng; Gabrielle M Baker; Vanessa C Bret-Mounet; Liza M Quintana; Lisa Frueh; Susan E Hankinson; Michelle D Holmes; Wendy Y Chen; Walter C Willett; Bernard Rosner Journal: Cancer Epidemiol Biomarkers Prev Date: 2022-10-04 Impact factor: 4.090
Authors: George Papaxoinis; Vassiliki Kotoula; Zoi Alexopoulou; Konstantine T Kalogeras; Flora Zagouri; Eleni Timotheadou; Helen Gogas; George Pentheroudakis; Christos Christodoulou; Angelos Koutras; Dimitrios Bafaloukos; Gerasimos Aravantinos; Pavlos Papakostas; Elpida Charalambous; Kyriaki Papadopoulou; Ioannis Varthalitis; Ioannis Efstratiou; Thomas Zaramboukas; Helen Patsea; Chrisoula D Scopa; Maria Skondra; Paris Kosmidis; Dimitrios Pectasides; George Fountzilas Journal: PLoS One Date: 2015-10-09 Impact factor: 3.240