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p-mTOR expression is associated with better prognosis in luminal breast carcinoma
  1. Francisco Beca1,2,3,
  2. Rosario Andre4,5,
  3. Duarte Saraiva Martins6,
  4. Tiago Bilhim7,
  5. Diana Martins2,
  6. Fernando Schmitt2,8,9
  1. 1Department of Medical Oncology, Dana-Farber Cancer Institute/Harvard Medical School, Boston, Massachusetts, USA
  2. 2IPATIMUP—Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
  3. 3Faculty of Medicine, Department of Pathology and Oncology, University of Porto, Porto, Portugal
  4. 4Champalimaud Clinical Centre, Champalimaud Foundation, Lisbon, Portugal
  5. 5Department of Genetics, Oncology and Human Toxicology, Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal
  6. 6Department of Pediatric Cardiology, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal
  7. 7Department of Radiology, Faculdade de Ciências Médicas, Universidade Nova de Lisboa and Hospital de São José, Centro Hospitalar de Lisboa Central, Lisbon, Portugal
  8. 8Faculty of Medicine, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
  9. 9Department of Pathology, University Health Network, Toronto, Canada
  1. Correspondence to Dr Fernando Schmitt, Faculty of Medicine, Department of Laboratory Medicine & Pathobiology, University of Toronto, University Health Network, Toronto General Hospital, 200 Elizabeth Street, 11E-215B, Toronto, Ontario, Canada M5G 2C4; fernando.schmitt{at}ipatimup.pt

Abstract

Aims 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.

  • BREAST CANCER
  • BREAST PATHOLOGY
  • SURGICAL PATHOLOGY

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