Silvestri V 1 , Barrowdale D 2 , Mulligan AM 3 , Neuhausen SL 4 , Fox S 5 , Karlan BY 6 Show all authors , Mitchell G 7 , James P 8 , Thull DL 9 , Zorn KK 10 , Carter NJ 11 , Nathanson KL 12 , Domchek SM 13 , Rebbeck TR 14 , Ramus SJ 15 , Nussbaum RL 16 , Olopade OI 17 , Rantala J 18 , Yoon SY 19 , Caligo MA 20 , Spugnesi L 21 , Bojesen A 22 , Pedersen IS 23 , Thomassen M 24 , Jensen UB 25 , Toland AE 26 , Senter L 27 , Andrulis IL 28 , Glendon G 29 , Hulick PJ 30 , Imyanitov EN 31 , Greene MH 32 , Mai PL 33 , Singer CF 34 , Rappaport-Fuerhauser C 35 , Kramer G 36 , Vijai J 37 , Offit K 38 , Robson M 39 , Lincoln A 40 , Jacobs L 41 , Machackova E 42 , Foretova L 43 , Navratilova M 44 , Vasickova P 45 , Couch FJ 46 , Hallberg E 47 , Ruddy KJ 48 , Sharma P 49 , Kim SW 50 , kConFab Investigators , Teixeira MR 51 , Pinto P 52 , Montagna M 53 , Matricardi L 54 , Arason A 55 , Johannsson OT 56 , Barkardottir RB 57 , Jakubowska A 58 , Lubinski J 59 , Izquierdo A 60 , Pujana MA 61 , Balmaña J 62 , Diez O 63 , Ivady G 64 , Papp J 65 , Olah E 66 , Kwong A 67 , Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) , Nevanlinna H 68 , Aittomäki K 69 , Perez Segura P 70 , Caldes T 71 , Van Maerken T 72 , Poppe B 73 , Claes KB 74 , Isaacs C 75 , Elan C 76 , Lasset C 77 , Stoppa-Lyonnet D 78 , Barjhoux L 79 , Belotti M 80 , Meindl A 81 , Gehrig A 82 , Sutter C 83 , Engel C 84 , Niederacher D 85 , Steinemann D 86 , Hahnen E 87 , Kast K 88 , Arnold N 89 , Varon-Mateeva R 90 , Wand D 91 , Godwin AK 92 , Evans DG 93 , Frost D 94 , Perkins J 95 , Adlard J 96 , Izatt L 97 , Platte R 98 , Eeles R 99 , Ellis S 100 , EMBRACE , Hamann U 101 , Garber J 102 , Fostira F 103 , Fountzilas G 104 , Pasini B 105 , Giannini G 106 , Rizzolo P 107 , Russo A 108 , Cortesi L 109 , Papi L 110 , Varesco L 111 , Palli D 112 , Zanna I 113 , Savarese A 114 , Radice P 115 , Manoukian S 116 , Peissel B 117 , Barile M 118 , Bonanni B 119 , Viel A 120 , Pensotti V 121 , Tommasi S 122 , Peterlongo P 123 , Weitzel JN 124 , Osorio A 125 , Benitez J 126 , McGuffog L 127 , Healey S 128 , Gerdes AM 129 , Ejlertsen B 130 , Hansen TV 131 , Steele L 132 , Ding YC 133 , Tung N 134 , Janavicius R 135 , Goldgar DE 136 , Buys SS 137 , Daly MB 138 , Bane A 139 , Terry MB 140 , John EM 141 , Southey M 142 , Easton DF 143 , Chenevix-Trench G 144 , Antoniou AC 145 , Ottini L 146

Affiliations 

  • 1 Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy. valentina.silvestri@uniroma1.it
  • 2 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK. daniel@srl.cam.ac.uk
  • 3 Laboratory Medicine Program, University Health Network, Toronto, ON, Canada. annamarie.mulligan@uhn.ca
  • 4 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA. sneuhausen@coh.org
  • 5 Peter MacCallum Cancer Institute, East Melbourne, Australia. stephen.fox@petermac.org
  • 6 Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. beth.karlan@cshs.org
  • 7 Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Australia. gillian.mitchell@petermac.org
  • 8 Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Australia. paul.james@petermac.org
  • 9 University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. dthull@magee.edu
  • 10 University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. kkzorn@uams.edu
  • 11 UPMC Cancer Center, Pittsburgh, PA, USA. engeln@upmc.edu
  • 12 Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA, USA. knathans@exchange.upenn.edu
  • 13 Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA, USA. susan.domchek@uphs.upenn.edu
  • 14 Department of Epidemiology and Biostatistics, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. rebbeck@exchange.upenn.edu
  • 15 Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA. sramus@usc.edu
  • 16 Department of Medicine and Genetics, University of California, San Francisco, San Francisco, CA, USA. nussbaumr@humgen.ucsf.edu
  • 17 Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, IL, USA. folopade@medicine.bsd.uchicago.edu
  • 18 Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. johanna.rantala@karolinska.se
  • 19 Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia. sookyee.yoon@carif.com.my
  • 20 Section of Genetic Oncology, Department of Laboratory Medicine, University of Pisa and University Hospital of Pisa, Pisa, Italy. adelaide.caligo@do.unipi.it
  • 21 Section of Genetic Oncology, Department of Laboratory Medicine, University of Pisa and University Hospital of Pisa, Pisa, Italy. laura.spugnesi@gmail.com
  • 22 Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark. anders.bojesen@slb.regionsyddanmark.dk
  • 23 Section of Molecular Diagnostics, Department of Biochemistry, Aalborg University Hospital, Aalborg, Denmark. isp@rn.dk
  • 24 Department of Clinical Genetics, Odense University Hospital, Odense C, Denmark. mads.thomassen@rsyd.dk
  • 25 Department of Clinical Genetics, Aarhus University Hospital, Aarhus N, Denmark. uffejens@rm.dk
  • 26 Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, OH, USA. amanda.toland@osumc.edu
  • 27 Division of Human Genetics, Department of Internal Medicine, The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA. leigha.senter@osumc.edu
  • 28 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. andrulis@lunenfeld.ca
  • 29 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada. gord.glendon@cancercare.on.ca
  • 30 Center for Medical Genetics, North Shore University Health System, Evanston, IL, USA. phulick@northshore.org
  • 31 N.N. Petrov Institute of Oncology, St. Petersburg, Russia. evgeny@imyanitov.spb.ru
  • 32 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. greenem@mail.nih.gov
  • 33 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. maip@mail.nih.gov
  • 34 Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. christian.singer@meduniwien.ac.at
  • 35 Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. christine.rappaport@akhwien.at
  • 36 Department of Urology, Medical University of Vienna, Vienna, Austria. gero.kramer@meduniwien.ac.at
  • 37 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. josephv@mskcc.org
  • 38 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. offitk@mskcc.org
  • 39 Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. robsonm@mskcc.org
  • 40 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. lincolna@mskcc.org
  • 41 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. jacobsl@mskcc.org
  • 42 Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic. emachack@mou.cz
  • 43 Masaryk Memorial Cancer Institute and Faculty of Medicine, Masaryk University, Brno, Czech Republic. foretova@mou.cz
  • 44 Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic. mnavrati@mou.cz
  • 45 Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic. vasickova@mou.cz
  • 46 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. couch.fergus@mayo.edu
  • 47 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. hallberg.emily@mayo.edu
  • 48 Department of Oncology, Mayo Clinic, Rochester, MN, USA. ruddy.kathryn@mayo.edu
  • 49 Department of Hematology and Oncology, University of Kansas Medical Center, Kansas City, KS, USA. psharma2@kumc.edu
  • 50 Department of Surgery, Daerim St. Mary's Hospital, Seoul, Korea. brcakorea@gmail.com
  • 51 Department of Genetics, Portuguese Institute of Oncology, Porto, Portugal. manuel.teixeira@ipoporto.min-saude.pt
  • 52 Department of Genetics, Portuguese Institute of Oncology, Porto, Portugal. pedro.pinto@ipoporto.min-saude.pt
  • 53 Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS (Scientific Institute of Hospitalization and Care), Padua, Italy. montagna@unipd.it
  • 54 Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS (Scientific Institute of Hospitalization and Care), Padua, Italy. laura.matricardi@ioveneto.it
  • 55 Department of Pathology, Landspitali University Hospital and Biomedical Centre (BMC), Faculty of Medicine, University of Iceland, Reykjavik, Iceland. adalgeir@landspitali.is
  • 56 Department of Oncology, Landspitali University Hospital and Faculty of Medicine, University of Iceland, Reykjavik, Iceland. oskarjoh@landspitali.is
  • 57 Department of Pathology, Landspitali University Hospital and Biomedical Centre (BMC), Faculty of Medicine, University of Iceland, Reykjavik, Iceland. rosa@landspitali.is
  • 58 Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. aniaj@pum.edu.pl
  • 59 Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. lubinski@pum.edu.pl
  • 60 Genetic Counseling Unit, Hereditary Cancer Program, Biomedical Research Institute of Girona (IDIBGI), Catalan Institute of Oncology, Girona, Spain. aizquierdo@iconcologia.net
  • 61 Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology, Barcelona, Spain. mapujana@iconcologia.net
  • 62 Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain. jbalmana@vhebron.net
  • 63 Oncogenetics Group, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO) and Universitat Autònoma de Barcelona, Barcelona, Spain. odiez@vhebron.net
  • 64 Department of Pathology, National Institute of Oncology, Budapest, Hungary. ivadygabi@oncol.hu
  • 65 Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary. janos.papp@oncol.hu
  • 66 Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary. e.olah@oncol.hu
  • 67 The Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong, China. akwong@asiabreastregistry.com
  • 68 Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. heli.nevanlinna@hus.fi
  • 69 Department of Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. kristiina.aittomaki@hus.fi
  • 70 Department of Oncology, San Carlos Clinical Hospital Health Research Institute (IdISSC), San Carlos Clinical Hospital, Madrid, Spain. pperez.hcsc@salud.madrid.org
  • 71 Molecular Oncology Laboratory, San Carlos Clinical Hospital Health Research Institute (IdISSC), San Carlos Clinical Hospital, Madrid, Spain. trinidad.caldes@salud.madrid.org
  • 72 Center for Medical Genetics, Ghent University, Ghent, Belgium. tom.vanmaerken@ugent.be
  • 73 Center for Medical Genetics, Ghent University, Ghent, Belgium. bruce.poppe@ugent.be
  • 74 Center for Medical Genetics, Ghent University, Ghent, Belgium. Kathleen.Claes@UGent.be
  • 75 Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. isaacsc@georgetown.edu
  • 76 Department of Tumour Biology, Institut Curie, Paris, France. camille.elan@curie.net
  • 77 CNRS UMR5558, Université Lyon 1, Lyon, France. christine.lasset@lyon.unicancer.fr
  • 78 Department of Tumour Biology, Institut Curie, Paris, France. dominique.stoppa-lyonnet@curie.net
  • 79 INSERM U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Université Lyon, Lyon, France. laure.barjhoux@lyon.unicancer.fr
  • 80 Department of Tumour Biology, Institut Curie, Paris, France. muriel.belotti@curie.net
  • 81 Department of Gynaecology and Obstetrics, Technical University of Munich, Munich, Germany. alfons.meindl@lrz.tu-muenchen.de
  • 82 Institute of Human Genetics, University of Wurzburg, Wurzburg, Germany. gehrig@biozentrum.uni-wuerzburg.de
  • 83 Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany. c.sutter@med.uni-heidelberg.de
  • 84 Institute for Medical Informatics, Statistics and Epidemiology University of Leipzig, Leipzig, Germany. christoph.engel@imise.uni-leipzig.de
  • 85 University of Dusseldorf, Dusseldorf, Germany. niederac@uni-duesseldorf.de
  • 86 Hannover Medical School, Hannover, Germany. steinemann.doris@mh-hannover.de
  • 87 Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO) and Center for Molecular Medicine Cologne (CMMC), Medical Faculty, University of Cologne and University Hospital Cologne, Cologne, Germany. eric.hahnen@uk-koeln.de
  • 88 Department of Gynecology and Obstetrics, Technical University of Dresden, Dresden, Germany. karin.kast@uniklinikum-dresden.de
  • 89 Department of Gynaecolgy and Obstetrics, University Hospital of Schleswig-Holstein, Christian-Albrechts-University of Kiel, Kiel, Germany. norbert.arnold@uksh.de
  • 90 Institute of Human Genetics, Charité, Berlin, Germany. raymonda.varon-mateeva@charite.de
  • 91 Institute of Human Genetics, Leipzig, Germany. dorothea.wand@medizin.uni-leipzig.de
  • 92 Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA. agodwin@kumc.edu
  • 93 Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK. gareth.evans@cmft.nhs.uk
  • 94 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK. djsf2@medschl.cam.ac.uk
  • 95 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK. jp410@medschl.cam.ac.uk
  • 96 Yorkshire Regional Genetics Service, Leeds, UK. julian.adlard@leedsth.nhs.uk
  • 97 Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, London, UK. louise.izatt@gstt.nhs.uk
  • 98 Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK. rp356@medschl.cam.ac.uk
  • 99 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany. rosalind.eeles@icr.ac.uk
  • 100 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK. steve@srl.cam.ac.uk
  • 101 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany. u.hamann@dkfz-heidelberg.de
  • 102 Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, MA, USA. judy_garber@dfci.harvard.edu
  • 103 Molecular Diagnostics Laboratory, Institute of Nuclear and Radiological Sciences and Technology (INRASTES), National Centre for Scientific Research "Demokritos", Aghia Paraskevi Attikis, Athens, Greece. florentia@rrp.demokritos.gr
  • 104 Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece. fountzil@auth.gr
  • 105 Department of Medical Science, University of Turin, Turin, Italy. barbara.pasini@unito.it
  • 106 Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy. giuseppe.giannini@uniroma1.it
  • 107 Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy. piera.rizzolo@uniroma1.it
  • 108 Section of Medical Oncology, Department of Surgical and Oncological Sciences, University of Palermo, Palermo, Italy. lab-oncobiologia@usa.net
  • 109 Department of Oncology and Haematology, University of Modena and Reggio Emilia, Modena, Italy. hbc@unimore.it
  • 110 Unit of Medical Genetics, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy. laura.papi@unifi.it
  • 111 Unit of Hereditary Cancer, Department of Epidemiology, Prevention and Special Functions, IRCCS (Scientific Institute of Hospitalization and Care), AOU San Martino - IST National Institute for Cancer Research, Genoa, Italy. liliana.varesco@hsanmartino.it
  • 112 Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy. d.palli@ispo.toscana.it
  • 113 Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy. i.zanna@ispo.toscana.it
  • 114 Unit of Genetic Counselling, Medical Oncology Department, Regina Elena National Cancer Institute, Rome, Italy. savarese@ifo.it
  • 115 Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, IRCCS (Scientific Institute of Hospitalization and Care), National Cancer Institute (INT), 20133, Milan, Italy. paolo.radice@istitutotumori.mi.it
  • 116 Unit of Medical Genetics, Department of Preventive and Predictive Medicine, IRCCS (Scientific Institute of Hospitalization and Care), National Cancer Institute (INT), Milan, Italy. siranoush.manoukian@istitutotumori.mi.it
  • 117 Unit of Medical Genetics, Department of Preventive and Predictive Medicine, IRCCS (Scientific Institute of Hospitalization and Care), National Cancer Institute (INT), Milan, Italy. bernard.peissel@istitutotumori.mi.it
  • 118 Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO), Milan, Italy. monica.barile@ieo.it
  • 119 Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO), Milan, Italy. bernardo.bonanni@ieo.it
  • 120 Division of Experimental Oncology, CRO Aviano National Cancer Institute, Aviano, PN, Italy. aviel@cro.it
  • 121 IFOM, FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy. valeria.pensotti@ifom.eu
  • 122 National Cancer Institute "Giovanni Paolo II", Bari, Italy. s.tommasi@oncologico.bari.it
  • 123 IFOM, FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy. paolo.peterlongo@ifom.eu
  • 124 Clinical Cancer Genetics, City of Hope Clinical Cancer Genetics Community Research Network, Duarte, CA, USA. jweitzel@coh.org
  • 125 Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), Madrid, Spain. aosorio@cnio.es
  • 126 Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain. jbenitez@cnio.es
  • 127 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK. lesley@srl.cam.ac.uk
  • 128 Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Australia. sue.healey@qimrberghofer.edu.au
  • 129 Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. anne-marie.gerdes@regionh.dk
  • 130 Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. bent.ejlertsen@regionh.dk
  • 131 Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. tvoh@rh.dk
  • 132 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA. lsteele@coh.org
  • 133 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA. ycding@coh.org
  • 134 Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA. ntung@bidmc.harvard.edu
  • 135 State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania. ramunas.janavicius@santa.lt
  • 136 Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA. david.goldgar@hsc.utah.edu
  • 137 Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA. saundra.buys@hci.utah.edu
  • 138 Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA. mary.daly@fccc.edu
  • 139 Department of Pathology & Molecular Medicine, Juravinski Hospital and Cancer Centre, McMaster University, Hamilton, ON, Canada. bane@hhsc.ca
  • 140 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. mt146@cumc.columbia.edu
  • 141 Department of Epidemiology, Cancer Prevention Institute of California, Fremont, CA, USA. esther.john@cpic.org
  • 142 Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, Australia. msouthey@unimelb.edu.au
  • 143 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK. douglas@srl.cam.ac.uk
  • 144 Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Australia. georgia.trench@qimrberghofer.edu.au
  • 145 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK. antonis@srl.cam.ac.uk
  • 146 Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy. laura.ottini@uniroma1.it
Breast Cancer Res., 2016 Feb 09;18(1):15.
PMID: 26857456 DOI: 10.1186/s13058-016-0671-y

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.