{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T17:40:02Z","timestamp":1758822002480,"version":"3.44.0"},"reference-count":26,"publisher":"BMJ","issue":"11","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2014,7,4]]},"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>43.8% of the tumours were positive for p-mTOR, with a significant correlation between p-mTOR expression with smaller (&lt;2\u2005cm) (p=0.021) and lower-grade tumours (p&lt;0.001). Expression of p-mTOR was also associated with longer DFS (HR of 0.32, p&lt;0.001) and OS (HR of 0.20, p&lt;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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jclinpath-2014-202320","type":"journal-article","created":{"date-parts":[[2014,7,23]],"date-time":"2014-07-23T03:24:05Z","timestamp":1406085845000},"page":"961-967","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["p-mTOR expression is associated with better prognosis in luminal breast carcinoma"],"prefix":"10.1136","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4409-012X","authenticated-orcid":false,"given":"Francisco","family":"Beca","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute\/Harvard Medical School, Boston, Massachusetts, USA"},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"},{"name":"Faculty of Medicine, Department of Pathology and Oncology, University of Porto, Porto, Portugal"}]},{"given":"Rosario","family":"Andre","sequence":"additional","affiliation":[{"name":"Champalimaud Clinical Centre, Champalimaud Foundation, Lisbon, Portugal"},{"name":"Department of Genetics, Oncology and Human Toxicology, Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal"}]},{"given":"Duarte Saraiva","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal"}]},{"given":"Tiago","family":"Bilhim","sequence":"additional","affiliation":[{"name":"Department of Radiology, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa and Hospital de S\u00e3o Jos\u00e9, Centro Hospitalar de Lisboa Central, Lisbon, Portugal"}]},{"given":"Diana","family":"Martins","sequence":"additional","affiliation":[{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"}]},{"given":"Fernando","family":"Schmitt","sequence":"additional","affiliation":[{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"},{"name":"Faculty of Medicine, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada"},{"name":"Department of Pathology, University Health Network, Toronto, Canada"}]}],"member":"239","published-online":{"date-parts":[[2014,7,22]]},"reference":[{"key":"2025092510032686000_67.11.961.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2672"},{"key":"2025092510032686000_67.11.961.2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04869"},{"key":"2025092510032686000_67.11.961.3","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4892(03)00071-7"},{"key":"2025092510032686000_67.11.961.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1109653"},{"key":"2025092510032686000_67.11.961.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa066838"},{"key":"2025092510032686000_67.11.961.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61039-9"},{"key":"2025092510032686000_67.11.961.7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2010.03570.x"},{"key":"2025092510032686000_67.11.961.8","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800525"},{"key":"2025092510032686000_67.11.961.9","first-page":"806","article-title":"Phosphorylated mTOR expression correlates with poor outcome in early-stage triple negative breast carcinomas","volume":"5","author":"Ueng","year":"2012","journal-title":"Int J Clin Exp Pathol"},{"key":"2025092510032686000_67.11.961.10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1991.tb00229.x"},{"key":"2025092510032686000_67.11.961.11","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2012-201169"},{"key":"2025092510032686000_67.11.961.12","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.50.9984"},{"key":"2025092510032686000_67.11.961.13","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt303"},{"key":"2025092510032686000_67.11.961.14","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djp335"},{"key":"2025092510032686000_67.11.961.15","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.01.0454"},{"key":"2025092510032686000_67.11.961.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2007.11.008"},{"key":"2025092510032686000_67.11.961.17","unstructured":"Lakhani SR Ellis I Schnitt S . 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