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. 2016 Feb 9;18(1):15.
doi: 10.1186/s13058-016-0671-y.

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

Valentina Silvestri  1 , Daniel Barrowdale  2 , Anna Marie Mulligan  3   4 , Susan L Neuhausen  5 , Stephen Fox  6 , Beth Y Karlan  7 , Gillian Mitchell  8   9 , Paul James  10   11 , Darcy L Thull  12 , Kristin K Zorn  13 , Natalie J Carter  14 , Katherine L Nathanson  15 , Susan M Domchek  16 , Timothy R Rebbeck  17 , Susan J Ramus  18 , Robert L Nussbaum  19 , Olufunmilayo I Olopade  20 , Johanna Rantala  21 , Sook-Yee Yoon  22   23 , Maria A Caligo  24 , Laura Spugnesi  25 , Anders Bojesen  26 , Inge Sokilde Pedersen  27 , Mads Thomassen  28 , Uffe Birk Jensen  29 , Amanda Ewart Toland  30 , Leigha Senter  31 , Irene L Andrulis  32   33   34 , Gord Glendon  35 , Peter J Hulick  36 , Evgeny N Imyanitov  37 , Mark H Greene  38 , Phuong L Mai  39 , Christian F Singer  40 , Christine Rappaport-Fuerhauser  41 , Gero Kramer  42 , Joseph Vijai  43 , Kenneth Offit  44 , Mark Robson  45 , Anne Lincoln  46 , Lauren Jacobs  47 , Eva Machackova  48 , Lenka Foretova  49 , Marie Navratilova  50 , Petra Vasickova  51 , Fergus J Couch  52   53 , Emily Hallberg  54 , Kathryn J Ruddy  55 , Priyanka Sharma  56 , Sung-Won Kim  57 ; kConFab Investigators; Manuel R Teixeira  58   59 , Pedro Pinto  60 , Marco Montagna  61 , Laura Matricardi  62 , Adalgeir Arason  63 , Oskar Th Johannsson  64 , Rosa B Barkardottir  65 , Anna Jakubowska  66 , Jan Lubinski  67 , Angel Izquierdo  68 , Miguel Angel Pujana  69 , Judith Balmaña  70 , Orland Diez  71 , Gabriella Ivady  72 , Janos Papp  73 , Edith Olah  74 , Ava Kwong  75   76 ; Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON); Heli Nevanlinna  77 , Kristiina Aittomäki  78 , Pedro Perez Segura  79 , Trinidad Caldes  80 , Tom Van Maerken  81 , Bruce Poppe  82 , Kathleen B M Claes  83 , Claudine Isaacs  84 , Camille Elan  85 , Christine Lasset  86   87 , Dominique Stoppa-Lyonnet  88   89 , Laure Barjhoux  90 , Muriel Belotti  91 , Alfons Meindl  92 , Andrea Gehrig  93 , Christian Sutter  94 , Christoph Engel  95 , Dieter Niederacher  96 , Doris Steinemann  97 , Eric Hahnen  98 , Karin Kast  99 , Norbert Arnold  100 , Raymonda Varon-Mateeva  101 , Dorothea Wand  102 , Andrew K Godwin  103 , D Gareth Evans  104 , Debra Frost  105 , Jo Perkins  106 , Julian Adlard  107 , Louise Izatt  108 , Radka Platte  109 , Ros Eeles  110 , Steve Ellis  111 ; EMBRACE; Ute Hamann  112 , Judy Garber  113 , Florentia Fostira  114 , George Fountzilas  115 , Barbara Pasini  116   117 , Giuseppe Giannini  118 , Piera Rizzolo  119 , Antonio Russo  120 , Laura Cortesi  121 , Laura Papi  122 , Liliana Varesco  123 , Domenico Palli  124 , Ines Zanna  125 , Antonella Savarese  126 , Paolo Radice  127 , Siranoush Manoukian  128 , Bernard Peissel  129 , Monica Barile  130 , Bernardo Bonanni  131 , Alessandra Viel  132 , Valeria Pensotti  133   134 , Stefania Tommasi  135 , Paolo Peterlongo  136 , Jeffrey N Weitzel  137 , Ana Osorio  138   139 , Javier Benitez  140   141   142 , Lesley McGuffog  143 , Sue Healey  144 , Anne-Marie Gerdes  145 , Bent Ejlertsen  146 , Thomas V O Hansen  147 , Linda Steele  148 , Yuan Chun Ding  149 , Nadine Tung  150 , Ramunas Janavicius  151 , David E Goldgar  152 , Saundra S Buys  153 , Mary B Daly  154 , Anita Bane  155 , Mary Beth Terry  156 , Esther M John  157 , Melissa Southey  158 , Douglas F Easton  159 , Georgia Chenevix-Trench  160 , Antonis C Antoniou  161 , Laura Ottini  162
Collaborators, Affiliations

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

Valentina Silvestri et al. Breast Cancer Res. .

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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Figures

Fig. 1
Fig. 1
Age-specific proportion of BRCA2 (breast cancer 2, early onset gene) male breast cancers according to pathologic characteristics. a Grade. b Oestrogen receptor (ER) status. c Progesterone receptor (PR) status. d Human epidermal growth factor receptor 2 (HER2) status. Error bars represent confidence intervals associated with each proportion
See this image and copyright information in PMC

References

    1. Ly D, Forman D, Ferlay J, Brinton LA, Cook MB. An international comparison of male and female breast cancer incidence rates. Int J Cancer. 2013;132(8):1918–1926. doi: 10.1002/ijc.27841. - DOI - PMC - PubMed
    1. Korde LA, Zujewski JA, Kamin L, Giordano S, Domchek S, Anderson WF, et al. Multidisciplinary meeting on male breast cancer: summary and research recommendations. J Clin Oncol. 2010;28(12):2114–2122. doi: 10.1200/JCO.2009.25.5729. - DOI - PMC - PubMed
    1. Basham VM, Lipscombe JM, Ward JM, Gayther SA, Ponder BA, Easton DF, et al. BRCA1 and BRCA2 mutations in a population-based study of male breast cancer. Breast Cancer Res. 2002;4:R2. doi: 10.1186/bcr419. - DOI - PMC - PubMed
    1. Ottini L, Masala G, D’Amico C, Mancini B, Saieva C, Aceto G, et al. BRCA1 and BRCA2 mutation status and tumor characteristics in male breast cancer: a population-based study in Italy. Cancer Res. 2003;63(2):342–347. - PubMed
    1. Rizzolo P, Silvestri V, Tommasi S, Pinto R, Danza K, Falchetti M, et al. Male breast cancer: genetics, epigenetics, and ethical aspects. Ann Oncol. 2013;24 Suppl 8:viii75–viii82. - PubMed

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