BACKGROUND: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). METHODS: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)). CONCLUSIONS: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

AO Città della Salute e della Scienza Turin Italy

Biomedical Network on Rare Diseases Madrid Spain

Biomedical Sciences Institute University of Porto Porto Portugal

Breast Cancer and Systems Biology Unit Bellvitge Biomedical Research Institute Catalan Institute of Oncology Barcelona Spain

Cancer Division QIMR Berghofer Medical Research Institute Brisbane Australia

Cancer Research Initiatives Foundation Sime Darby Medical Centre Subang Jaya Malaysia

Cancer Risk and Prevention Clinic Dana Farber Cancer Institute Boston MA USA

Center for Clinical Cancer Genetics and Global Health University of Chicago Medical Center Chicago IL USA

Center for Genomic Medicine Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Center for Hereditary Breast and Ovarian Cancer Center for Integrated Oncology Medical Faculty University of Cologne and University Hospital Cologne Cologne Germany

Center for Medical Genetics Ghent University Ghent Belgium

Center for Medical Genetics North Shore University Health System Evanston IL USA

Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care School of Clinical Medicine University of Cambridge Cambridge UK

Clinical Cancer Genetics City of Hope Clinical Cancer Genetics Community Research Network Duarte CA USA

Clinical Genetics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD USA

Clinical Genetics Guy's and St Thomas' NHS Foundation Trust London UK

Clinical Genetics Service Department of Medicine Memorial Sloan Kettering Cancer Center New York NY USA

CNRS UMR5558 Université Lyon 1 Lyon France

Cogentech Cancer Genetic Test Laboratory Milan Italy

Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Clinical Genetics Aarhus University Hospital Aarhus N Denmark

Department of Clinical Genetics Fox Chase Cancer Center Philadelphia PA USA

Department of Clinical Genetics Karolinska University Hospital Stockholm Sweden

Department of Clinical Genetics Odense University Hospital Odense C Denmark

Department of Clinical Genetics Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Clinical Genetics University of Helsinki and Helsinki University Hospital Helsinki Finland

Department of Clinical Genetics Vejle Hospital Vejle Denmark

Department of Dermatology Huntsman Cancer Institute University of Utah School of Medicine Salt Lake City UT USA

Department of Epidemiology and Biostatistics Abramson Cancer Center Perelman School of Medicine University of Pennsylvania Philadelphia PA USA

Department of Epidemiology Cancer Prevention Institute of California Fremont CA USA

Department of Epidemiology Mailman School of Public Health Columbia University New York NY USA

Department of Genetics and Pathology Pomeranian Medical University Szczecin Poland

Department of Genetics Portuguese Institute of Oncology Porto Portugal

Department of Gynaecolgy and Obstetrics University Hospital of Schleswig Holstein Christian Albrechts University of Kiel Kiel Germany

Department of Gynaecology and Obstetrics Technical University of Munich Munich Germany

Department of Gynecology and Obstetrics Technical University of Dresden Dresden Germany

Department of Health Sciences Research Mayo Clinic Rochester MN USA

Department of Hematology and Oncology University of Kansas Medical Center Kansas City KS USA

Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON Canada

Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA

Department of Medical Oncology Beth Israel Deaconess Medical Center Boston MA USA

Department of Medical Oncology Papageorgiou Hospital Aristotle University of Thessaloniki School of Medicine Thessaloniki Greece

Department of Medical Oncology Vall d'Hebron University Hospital Barcelona Spain

Department of Medical Science University of Turin Turin Italy

Department of Medicine Abramson Cancer Center Perelman School of Medicine at The University of Pennsylvania Philadelphia PA USA

Department of Medicine and Genetics University of California San Francisco San Francisco CA USA

Department of Medicine Huntsman Cancer Institute University of Utah School of Medicine Salt Lake City UT USA

Department of Medicine Memorial Sloan Kettering Cancer Center New York NY USA

Department of Molecular Genetics National Institute of Oncology Budapest Hungary

Department of Molecular Genetics University of Toronto Toronto ON Canada

Department of Molecular Medicine Sapienza University of Rome Viale Regina Elena 324 00161 Rome Italy

Department of Molecular Virology Immunology and Medical Genetics College of Medicine The Ohio State University Columbus OH USA

Department of Obstetrics and Gynecology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Obstetrics and Gynecology University of Helsinki and Helsinki University Hospital Helsinki Finland

Department of Oncology and Haematology University of Modena and Reggio Emilia Modena Italy

Department of Oncology Landspitali University Hospital and Faculty of Medicine University of Iceland Reykjavik Iceland

Department of Oncology Mayo Clinic Rochester MN USA

Department of Oncology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Oncology San Carlos Clinical Hospital Health Research Institute San Carlos Clinical Hospital Madrid Spain

Department of Oncology The University of Melbourne Melbourne VIC Australia

Department of Pathology and Laboratory Medicine University of Kansas Medical Center Kansas City KS USA

Department of Pathology and Molecular Medicine Juravinski Hospital and Cancer Centre McMaster University Hamilton ON Canada

Department of Pathology Landspitali University Hospital and Biomedical Centre Faculty of Medicine University of Iceland Reykjavik Iceland

Department of Pathology National Institute of Oncology Budapest Hungary

Department of Population Sciences Beckman Research Institute of City of Hope Duarte CA USA

Department of Preventive Medicine Keck School of Medicine University of Southern California Norris Comprehensive Cancer Center Los Angeles CA USA

Department of Surgery Daerim St Mary's Hospital Seoul Korea

Department of Surgery The University of Hong Kong Hong Kong China

Department of Tumour Biology Institut Curie Paris France

Department of Urology Medical University of Vienna Vienna Austria

Division of Cancer Prevention and Genetics European Institute of Oncology Milan Italy

Division of Experimental Oncology CRO Aviano National Cancer Institute Aviano PN Italy

Division of Human Genetics Department of Internal Medicine The Comprehensive Cancer Center The Ohio State University Columbus OH USA

Familial Cancer Centre Peter MacCallum Cancer Centre Melbourne Australia

Genetic Counseling Unit Hereditary Cancer Program Biomedical Research Institute of Girona Catalan Institute of Oncology Girona Spain

Genetic Epidemiology Laboratory Department of Pathology University of Melbourne Parkville Australia

Genetic Medicine Manchester Academic Health Sciences Centre Central Manchester University Hospitals NHS Foundation Trust Manchester UK

Hannover Medical School Hannover Germany

Human Genetics Group Human Cancer Genetics Program Spanish National Cancer Centre Madrid Spain

Human Genetics Group Spanish National Cancer Centre Madrid Spain

Human Genotyping Madrid Spain

IFOM FIRC Institute of Molecular Oncology Milan Italy

Immunology and Molecular Oncology Unit Veneto Institute of Oncology IOV IRCCS Padua Italy

INSERM U1052 CNRS UMR5286 Centre de Recherche en Cancérologie de Lyon Université Lyon Lyon France

Institute for Medical Informatics Statistics and Epidemiology University of Leipzig Leipzig Germany

Institute of Human Genetics Charité Berlin Germany

Institute of Human Genetics Leipzig Germany

Institute of Human Genetics University Hospital Heidelberg Heidelberg Germany

Institute of Human Genetics University of Wurzburg Wurzburg Germany

Laboratory Medicine Program University Health Network Toronto ON Canada

Lombardi Comprehensive Cancer Center Georgetown University Washington DC USA

Lunenfeld Tanenbaum Research Institute Mount Sinai Hospital Toronto ON Canada

Masaryk Memorial Cancer Institute and Faculty of Medicine Masaryk University Brno Czech Republic

Molecular and Nutritional Epidemiology Unit Cancer Research and Prevention Institute Florence Italy

Molecular Diagnostics Laboratory Institute of Nuclear and Radiological Sciences and Technology National Centre for Scientific Research Demokritos Aghia Paraskevi Attikis Athens Greece

Molecular Genetics of Breast Cancer German Cancer Research Center Heidelberg Germany

Molecular Oncology Laboratory San Carlos Clinical Hospital Health Research Institute San Carlos Clinical Hospital Madrid Spain

N N Petrov Institute of Oncology St Petersburg Russia

National Cancer Institute Giovanni Paolo 2 Bari Italy

Oncogenetics Group Vall d'Hebron University Hospital Vall d'Hebron Institute of Oncology and Universitat Autònoma de Barcelona Barcelona Spain

Oncogenetics Team The Institute of Cancer Research and Royal Marsden NHS Foundation Trust Sutton UK

Peter MacCallum Cancer Institute East Melbourne Australia

Section of Genetic Oncology Department of Laboratory Medicine University of Pisa and University Hospital of Pisa Pisa Italy

Section of Medical Oncology Department of Surgical and Oncological Sciences University of Palermo Palermo Italy

Section of Molecular Diagnostics Department of Biochemistry Aalborg University Hospital Aalborg Denmark

State Research Institute Centre for Innovative Medicine Vilnius Lithuania

The Hong Kong Hereditary Breast Cancer Family Registry Cancer Genetics Center Hong Kong Sanatorium and Hospital Hong Kong China

Unit of Genetic Counselling Medical Oncology Department Regina Elena National Cancer Institute Rome Italy

Unit of Hereditary Cancer Department of Epidemiology Prevention and Special Functions IRCCS AOU San Martino IST National Institute for Cancer Research Genoa Italy

Unit of Medical Genetics Department of Biomedical Experimental and Clinical Sciences University of Florence Florence Italy

Unit of Medical Genetics Department of Preventive and Predictive Medicine IRCCS Milan Italy

Unit of Molecular Bases of Genetic Risk and Genetic Testing Department of Preventive and Predictive Medicine IRCCS 20133 Milan Italy

Unité de Prévention et d'Epidémiologie Génétique Centre Léon Bérard Lyon France

Université Paris Descartes Sorbonne Paris Cité Paris France

University Malaya Cancer Research Institute Faculty of Medicine University Malaya Medical Centre University Malaya Kuala Lumpur Malaysia

University of Dusseldorf Dusseldorf Germany

University of Pittsburgh School of Medicine Pittsburgh PA USA

UPMC Cancer Center Pittsburgh PA USA

Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute Cedars Sinai Medical Center Los Angeles CA USA

Yorkshire Regional Genetics Service Leeds UK

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Cancer Spectrum, Family History of Cancer and Overall Survival in Men with Germline BRCA1 or BRCA2 Mutations

Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants: Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)