title: Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2.
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.
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authors: IFOM, FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy. valeria.pensotti@ifom.eu.|Cogentech Cancer Genetic Test Laboratory, Milan, Italy. valeria.pensotti@ifom.eu.
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authors: Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain. jbenitez@cnio.es.|Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain. jbenitez@cnio.es.|Human Genotyping (CEGEN) Unit, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. jbenitez@cnio.es.
authors: Javier
authors: J
authors: Benitez
authors: 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.
authors: Lesley
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authors: McGuffog
authors: Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Australia. sue.healey@qimrberghofer.edu.au.
authors: Sue
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authors: Healey
authors: Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. anne-marie.gerdes@regionh.dk.
authors: Anne-Marie
authors: AM
authors: Gerdes
authors: Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. bent.ejlertsen@regionh.dk.
authors: Bent
authors: B
authors: Ejlertsen
authors: Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. tvoh@rh.dk.
authors: Thomas V O
authors: TV
authors: Hansen
authors: Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA. lsteele@coh.org.
authors: Linda
authors: L
authors: Steele
authors: Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA. ycding@coh.org.
authors: Yuan Chun
authors: YC
authors: Ding
authors: Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA. ntung@bidmc.harvard.edu.
authors: Nadine
authors: N
authors: Tung
authors: State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania. ramunas.janavicius@santa.lt.
authors: Ramunas
authors: R
authors: Janavicius
authors: Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA. david.goldgar@hsc.utah.edu.
authors: David E
authors: DE
authors: Goldgar
authors: Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA. saundra.buys@hci.utah.edu.
authors: Saundra S
authors: SS
authors: Buys
authors: Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA. mary.daly@fccc.edu.
authors: Mary B
authors: MB
authors: Daly
authors: Department of Pathology & Molecular Medicine, Juravinski Hospital and Cancer Centre, McMaster University, Hamilton, ON, Canada. bane@hhsc.ca.
authors: Anita
authors: A
authors: Bane
authors: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. mt146@cumc.columbia.edu.
authors: Mary Beth
authors: MB
authors: Terry
authors: Department of Epidemiology, Cancer Prevention Institute of California, Fremont, CA, USA. esther.john@cpic.org.
authors: Esther M
authors: EM
authors: John
authors: Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, Australia. msouthey@unimelb.edu.au.
authors: Melissa
authors: M
authors: Southey
authors: 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.
authors: Douglas F
authors: DF
authors: Easton
authors: Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Australia. georgia.trench@qimrberghofer.edu.au.
authors: Georgia
authors: G
authors: Chenevix-Trench
authors: 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.
authors: Antonis C
authors: AC
authors: Antoniou
authors: Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy. laura.ottini@uniroma1.it.
authors: Laura
authors: L
authors: Ottini
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; C551750:BRCA2 protein, human