Article open access publication

Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

Breast Cancer Research, Springer Nature, ISSN 1465-5411

Volume 18, 1, 2016

DOI:10.1186/s13058-016-0671-y, Dimensions: pub.1049716564, PMC: PMC4746828, PMID: 26857456,

Authors

James, Paul (6) (8)
Yoon, Sook-Yee (17) (18)
Kwong, Ava (45) (46)
Lasset, Christine (53) (54)
Eeles, Ros (72)
Pasini, Barbara (76) (77)
Pensotti, Valeria (87) (88)
Osorio, Ana (90) (91)
Benitez, Javier (90) (91)
Bane, Anita (100)

* Corresponding author

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  1. (1) Sapienza University of Rome, grid.7841.a
  2. (2) University of Cambridge, grid.5335.0
  3. (3) University Health Network, grid.231844.8
  4. (4) University of Toronto, grid.17063.33
  5. (5) City Of Hope National Medical Center, grid.410425.6
  6. (6) Peter MacCallum Cancer Centre, grid.1055.1
  7. (7) Cedars-Sinai Medical Center, grid.50956.3f
  8. (8) University of Melbourne, grid.1008.9
  9. (9) University of Pittsburgh, grid.21925.3d
  10. (10) University of Pittsburgh Medical Center, grid.412689.0
  11. (11) Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA, USA
  12. (12) University of Pennsylvania, grid.25879.31
  13. (13) University of Southern California, grid.42505.36
  14. (14) University of California, San Francisco, grid.266102.1
  15. (15) University of Chicago Medical Center, grid.412578.d
  16. (16) Karolinska University Hospital, grid.24381.3c
  17. (17) Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia
  18. (18) University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya Medical Centre, University Malaya, Kuala Lumpur, Malaysia
  19. (19) Azienda Ospedaliera Universitaria Pisana, grid.144189.1
  20. (20) Vejle Sygehus, grid.417271.6, Southern Denmark Region
  21. (21) Aalborg Hospital, grid.27530.33, North Denmark Region
  22. (22) Odense University Hospital, grid.7143.1, Southern Denmark Region
  23. (23) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  24. (24) The Ohio State University, grid.261331.4
  25. (25) Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
  26. (26) NorthShore University HealthSystem, grid.240372.0
  27. (27) Institute of Oncology NN Petrov, grid.465337.0
  28. (28) National Cancer Institute, grid.48336.3a
  29. (29) Medical University of Vienna, grid.22937.3d
  30. (30) Memorial Sloan Kettering Cancer Center, grid.51462.34
  31. (31) Masaryk Memorial Cancer Institute, grid.419466.8
  32. (32) Masaryk University, grid.10267.32
  33. (33) Mayo Clinic, grid.66875.3a
  34. (34) University of Kansas Medical Center, grid.412016.0
  35. (35) Seoul St. Mary's Hospital, grid.414966.8
  36. (36) University of Porto, grid.5808.5
  37. (37) Portuguese Oncology Institute, grid.418711.a
  38. (38) Istituto Oncologico Veneto, grid.419546.b
  39. (39) University of Iceland, grid.14013.37
  40. (40) Pomeranian Medical University, grid.107950.a
  41. (41) Institut d'Investigació Biomèdica de Girona, grid.429182.4
  42. (42) Breast Cancer and Systems Biology Unit, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology, Barcelona, Spain
  43. (43) Hospital Universitari Vall d'Hebron, grid.411083.f
  44. (44) National Institute of Oncology, grid.419617.c
  45. (45) Hong Kong Sanatorium and Hospital, grid.414329.9
  46. (46) University of Hong Kong, grid.194645.b
  47. (47) Helsinki University Central Hospital, grid.15485.3d
  48. (48) Department of Oncology, San Carlos Clinical Hospital Health Research Institute (IdISSC), San Carlos Clinical Hospital, Madrid, Spain
  49. (49) Molecular Oncology Laboratory, San Carlos Clinical Hospital Health Research Institute (IdISSC), San Carlos Clinical Hospital, Madrid, Spain
  50. (50) Ghent University, grid.5342.0
  51. (51) Georgetown University Medical Center, grid.411667.3
  52. (52) Institute Curie, grid.418596.7
  53. (53) Centre Léon Bérard, grid.418116.b
  54. (54) Claude Bernard University Lyon 1, grid.7849.2
  55. (55) Paris Descartes University, grid.10992.33
  56. (56) University of Lyon System, grid.25697.3f
  57. (57) Technical University of Munich, grid.6936.a
  58. (58) University of Würzburg, grid.8379.5
  59. (59) University Hospital Heidelberg, grid.5253.1
  60. (60) Leipzig University, grid.9647.c
  61. (61) Heinrich Heine University Düsseldorf, grid.411327.2
  62. (62) Hannover Medical School, grid.10423.34
  63. (63) University Hospital Cologne, grid.411097.a
  64. (64) TU Dresden, grid.4488.0
  65. (65) Department of Gynaecolgy and Obstetrics, University Hospital of Schleswig-Holstein, Christian-Albrechts-University of Kiel, Kiel, Germany
  66. (66) Charité, grid.6363.0
  67. (67) University of Bonn, grid.10388.32
  68. (68) Manchester University NHS Foundation Trust, grid.498924.a
  69. (69) Yorkshire Regional Genetics Service, Leeds, UK
  70. (70) Guy's and St Thomas' NHS Foundation Trust, grid.420545.2
  71. (71) Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK
  72. (72) German Cancer Research Center, grid.7497.d
  73. (73) Dana-Farber Cancer Institute, grid.65499.37
  74. (74) National Centre of Scientific Research Demokritos, grid.6083.d
  75. (75) Aristotle University of Thessaloniki, grid.4793.9
  76. (76) Azienda Ospedaliera Citta' Della Salute E Della Scienza Di Torino, grid.432329.d
  77. (77) University of Turin, grid.7605.4
  78. (78) University of Palermo, grid.10776.37
  79. (79) University of Modena and Reggio Emilia, grid.7548.e
  80. (80) University of Florence, grid.8404.8
  81. (81) Ospedale San Martino, grid.410345.7
  82. (82) Istituto per lo Studio e la Prevenzione Oncologica, grid.417623.5
  83. (83) Istituti Fisioterapici Ospitalieri, grid.417520.5
  84. (84) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  85. (85) European Institute of Oncology, grid.15667.33
  86. (86) Centro di Riferimento Oncologico, grid.418321.d
  87. (87) Cogentech Cancer Genetic Test Laboratory, Milan, Italy
  88. (88) IFOM, FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy
  89. (89) Clinical Cancer Genetics, City of Hope Clinical Cancer Genetics Community Research Network, Duarte, CA, USA
  90. (90) Centre for Biomedical Network Research on Rare Diseases, grid.452372.5
  91. (91) Spanish National Cancer Research Centre, grid.7719.8
  92. (92) QIMR Berghofer Medical Research Institute, grid.1049.c
  93. (93) Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  94. (94) Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  95. (95) Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  96. (96) Beth Israel Deaconess Medical Center, grid.239395.7
  97. (97) State Research Institute Centre for Innovative Medicine, grid.493509.2
  98. (98) University of Utah, grid.223827.e
  99. (99) Temple University Health System, grid.412530.1
  100. (100) McMaster University, grid.25073.33
  101. (101) Columbia University, grid.21729.3f
  102. (102) Cancer Prevention Institute of California, grid.280669.3

Description

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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Times Cited: 42

Field Citation Ratio (FCR): 13.98

Relative Citation ratio (RCR): 1.67

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