title: p-mTOR expression is associated with better prognosis in luminal breast carcinoma.
abstract: OBJECTIVE
  Despite considerable interest in the PI3K/AKT/mTOR pathway in breast carcinomas (BC), published data reports contradictory results regarding the association of phosphorylated mammalian target of Rapamycin (p-mTOR) expression with clinico-pathological features and prognosis in BC. Here, we evaluate the main clinico-pathological associations with p-mTOR expression in BC, with focus on the different molecular subtypes.
  
  
  METHODS
  In this retrospective study, 331 BC patients were included in final analysis. Outcome measures included disease-free survival (DFS) and overall survival (OS) times. Baseline data and outcome measures were compared between immunohistochemical p-mTOR expressing and non-expressing BCs. Subgroup analysis was performed to assess the effect of p-mTOR expression in the outcome for each BC molecular subtype.
  
  
  RESULTS
  43.8% of the tumours were positive for p-mTOR, with a significant correlation between p-mTOR expression with smaller (<2 cm) (p=0.021) and lower-grade tumours (p<0.001). Expression of p-mTOR was also associated with longer DFS (HR of 0.32, p<0.001) and OS (HR of 0.20, p<0.001). In a multivariable analysis, the HR remained significant with minimal change (HR=0.26, p=0.002 for OS; HR=0.40, p=0.002 for DFS). In subgroup analysis, luminal p-mTOR-expressing tumours demonstrated longer DFS and OS (HR 0.33, p=0.003; HR 0.20, p=0.003, respectively) independently of size, grade, lymph node status and Her-2 overexpression.
  
  
  CONCLUSIONS
  p-mTOR expression is associated with smaller, lower-grade and with luminal BC. In multivariable analysis, p-mTOR expression was associated with longer DFS and OS, independently of the size, grade and lymph node status, especially in luminal BCs.
authors: Department of Medical Oncology, Dana-Farber Cancer Institute/Harvard Medical School, Boston, Massachusetts, USA IPATIMUP-Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal Faculty of Medicine, Department of Pathology and Oncology, University of Porto, Porto, Portugal.
authors: Francisco
authors: http://orcid.org/0000-0002-4409-012X
authors: F
authors: Beca
authors: Champalimaud Clinical Centre, Champalimaud Foundation, Lisbon, Portugal Department of Genetics, Oncology and Human Toxicology, Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal.
authors: Rosario
authors: R
authors: Andre
authors: Department of Pediatric Cardiology, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal.
authors: Duarte Saraiva
authors: DS
authors: Martins
authors: Department of Radiology, Faculdade de Ciências Médicas, Universidade Nova de Lisboa and Hospital de São José, Centro Hospitalar de Lisboa Central, Lisbon, Portugal.
authors: Tiago
authors: T
authors: Bilhim
authors: IPATIMUP-Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
authors: Diana
authors: D
authors: Martins
authors: IPATIMUP-Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal Faculty of Medicine, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada Department of Pathology, University Health Network, Toronto, Canada.
authors: Fernando
authors: F
authors: Schmitt
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D010766:Phosphorylation; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D058570:TOR Serine-Threonine Kinases / Q000032:analysis*; D013997:Time Factors; D046888:Tissue Array Analysis; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: BREAST CANCER; BREAST PATHOLOGY; SURGICAL PATHOLOGY