title: Pathological characterisation of male breast cancer: Results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program.
abstract: Several prognostic histological features have been established in female breast cancer (BC), but it is unknown whether these can be extrapolated to male BC patients. The aim of this study was to evaluate the prognostic value of several histological features in a large series of male BC.
  
  
  
  Central pathology review was performed for 1483 male BCs collected through part 1 of the European Organisation for Research and Treatment of Cancer (EORTC) International Male BC Program. Pathology review included histological subtype, grade, mitotic activity index (MAI), presence of a fibrotic focus and density of tumour-infiltrating lymphocytes (TILs). These features were correlated with clinical outcome. The relationship between these features and surrogate molecular subtypes using immunohistochemistry was also assessed.
  
  
  
  Median follow-up for overall survival (OS) was 7.1 years. Overall histological grade was not significantly associated with OS (p = 0.129). MAI, the presence of a fibrotic focus and a low TIL density however were correlated with unfavourable OS (p = 0.023, p = 0.004 and p = 0.011, respectively). BC subtype correlated with TIL density (p = 0.015), as we observed a higher density for human epidermal growth factor receptor type 2 (HER2) positive BC compared to luminal HER2-negative subtype. No association was observed between subtype and fibrotic focus.
  
  
  
  Histologic grade was not significantly correlated with clinical outcome in this series, unlike what is seen in female patients. These results contribute to our understanding of male BC and indicate the importance of further research on the optimisation of risk stratification and treatment decisions for male BC patients.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marijn A
authors.initials: MA
authors.lastname: Vermeulen
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Slaets
authors.affiliation: Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal.
authors.forename: Fatima
authors.initials: F
authors.lastname: Cardoso
authors.affiliation: Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Sharon H
authors.initials: SH
authors.lastname: Giordano
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tryfonidis
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.affiliation: BOOG Study Center/Dutch Breast Cancer Research Group, Amsterdam, The Netherlands.
authors.forename: Nizet H
authors.initials: NH
authors.lastname: Dijkstra
authors.affiliation: BOOG Study Center/Dutch Breast Cancer Research Group, Amsterdam, The Netherlands; Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Carolien P
authors.initials: CP
authors.lastname: Schröder
authors.affiliation: BOOG Study Center/Dutch Breast Cancer Research Group, Amsterdam, The Netherlands; Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Christi J
authors.initials: CJ
authors.lastname: van Asperen
authors.affiliation: Swedish Association of Breast Oncologists (SABO), Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Barbro
authors.initials: B
authors.lastname: Linderholm
authors.affiliation: Department of Oncology, Cheltenham General Hospital, Gloucestershire, UK.
authors.forename: Kim
authors.initials: K
authors.lastname: Benstead
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Renee
authors.initials: R
authors.lastname: Foekens
authors.affiliation: Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands; BOOG Study Center/Dutch Breast Cancer Research Group, Amsterdam, The Netherlands.
authors.forename: John W M
authors.initials: JWM
authors.lastname: Martens
authors.affiliation: Diagnostic Development, Ontario Institute for Cancer Research, Toronto, Canada; Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Scotland, UK.
authors.forename: John M S
authors.initials: JMS
authors.lastname: Bartlett
authors.affiliation: BOOG Study Center/Dutch Breast Cancer Research Group, Amsterdam, The Netherlands; Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: c.h.m.vandeurzen@erasmusmc.nl.
authors.forename: Carolien H M
authors.initials: CHM
authors.lastname: van Deurzen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D018567:Breast Neoplasms, Male / Q000473:pathology*; D002277:Carcinoma / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology; D018275:Carcinoma, Lobular / Q000473:pathology; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor
keywords: Breast cancer; Fibrotic focus; Histological grade; Male; Tumour-infiltrating lymphocytes