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

Valentina Silvestri; Daniel Barrowdale; Anna Marie Mulligan; Susan L. Neuhausen; Stephen Fox; Beth Y. Karlan; Gillian Mitchell; Paul James; Darcy L. Thull; Kristin K. Zorn; Natalie J. Carter; Katherine L. Nathanson; Susan M. Domchek; Timothy R. Rebbeck; Susan J. Ramus; Robert L. Nussbaum; Olufunmilayo I. Olopade; Johanna Rantala; Sook Yee Yoon; Maria A. Caligo; Laura Spugnesi; Anders Bojesen; Inge Sokilde Pedersen; Mads Thomassen; Uffe Birk Jensen; Amanda Ewart Toland; Leigha Senter; Irene L. Andrulis; Gord Glendon; Peter J. Hulick; Evgeny N. Imyanitov; Mark H. Greene; Phuong L. Mai; Christian F. Singer; Christine Rappaport-Fuerhauser; Gero Kramer; Joseph Vijai; Kenneth Offit; Mark Robson; Anne Lincoln; Lauren Jacobs; Eva Machackova; Lenka Foretova; Marie Navratilova; Petra Vasickova; Fergus J. Couch; Emily Hallberg; Kathryn J. Ruddy; Priyanka Sharma; Sung Won Kim; Manuel R. Teixeira; Pedro Pinto; Marco Montagna; Laura Matricardi; Adalgeir Arason; Oskar Th Johannsson; Rosa B. Barkardottir; Anna Jakubowska; Jan Lubinski; Angel Izquierdo; Miguel Angel Pujana; Judith Balmaña; Orland Diez; Gabriella Ivady; Janos Papp; Edith Olah; Ava Kwong; Heli Nevanlinna; Kristiina Aittomäki; Pedro Perez Segura; Trinidad Caldes; Tom Van Maerken; Bruce Poppe; Kathleen B.M. Claes; Claudine Isaacs; Camille Elan; Christine Lasset; Dominique Stoppa-Lyonnet; Laure Barjhoux; Muriel Belotti; Alfons Meindl; Andrea Gehrig; Christian Sutter; Christoph Engel; Dieter Niederacher; Doris Steinemann; Eric Hahnen; Karin Kast; Norbert Arnold; Raymonda Varon-Mateeva; Dorothea Wand; Andrew K. Godwin; D. Gareth Evans; Debra Frost; Jo Perkins; Julian Adlard; Louise Izatt; Radka Platte; Ros Eeles; Steve Ellis; Ute Hamann; Judy Garber; Florentia Fostira; George Fountzilas; Barbara Pasini; Giuseppe Giannini; Piera Rizzolo; Antonio Russo; Laura Cortesi; Laura Papi; Liliana Varesco; Domenico Palli; Ines Zanna; Antonella Savarese; Paolo Radice; Siranoush Manoukian; Bernard Peissel; Monica Barile; Bernardo Bonanni; Alessandra Viel; Valeria Pensotti; Stefania Tommasi; Paolo Peterlongo; Jeffrey N. Weitzel; Ana Osorio; Javier Benitez; Lesley McGuffog; Sue Healey; Anne Marie Gerdes; Bent Ejlertsen; Thomas V.O. Hansen; Linda Steele; Yuan Chun Ding; Nadine Tung; Ramunas Janavicius; David E. Goldgar; Saundra S. Buys; Mary B. Daly; Anita Bane; Mary Beth Terry; Esther M. John; Melissa Southey; Douglas F. Easton; Georgia Chenevix-Trench; Antonis C. Antoniou; Laura Ottini

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, Daniel Barrowdale, Anna Marie Mulligan, Susan L. Neuhausen, Stephen Fox, Beth Y. Karlan, Gillian Mitchell, Paul James, Darcy L. Thull, Kristin K. Zorn, Natalie J. Carter, Katherine L. Nathanson, Susan M. Domchek, Timothy R. Rebbeck, Susan J. Ramus, Robert L. Nussbaum, Olufunmilayo I. Olopade, Johanna Rantala, Sook Yee Yoon, Maria A. CaligoLaura Spugnesi, Anders Bojesen, Inge Sokilde Pedersen, Mads Thomassen, Uffe Birk Jensen, Amanda Ewart Toland, Leigha Senter, Irene L. Andrulis, Gord Glendon, Peter J. Hulick, Evgeny N. Imyanitov, Mark H. Greene, Phuong L. Mai, Christian F. Singer, Christine Rappaport-Fuerhauser, Gero Kramer, Joseph Vijai, Kenneth Offit, Mark Robson, Anne Lincoln, Lauren Jacobs, Eva Machackova, Lenka Foretova, Marie Navratilova, Petra Vasickova, Fergus J. Couch, Emily Hallberg, Kathryn J. Ruddy, Priyanka Sharma, Sung Won Kim, Manuel R. Teixeira, Pedro Pinto, Marco Montagna, Laura Matricardi, Adalgeir Arason, Oskar Th Johannsson, Rosa B. Barkardottir, Anna Jakubowska, Jan Lubinski, Angel Izquierdo, Miguel Angel Pujana, Judith Balmaña, Orland Diez, Gabriella Ivady, Janos Papp, Edith Olah, Ava Kwong, Heli Nevanlinna, Kristiina Aittomäki, Pedro Perez Segura, Trinidad Caldes, Tom Van Maerken, Bruce Poppe, Kathleen B.M. Claes, Claudine Isaacs, Camille Elan, Christine Lasset, Dominique Stoppa-Lyonnet, Laure Barjhoux, Muriel Belotti, Alfons Meindl, Andrea Gehrig, Christian Sutter, Christoph Engel, Dieter Niederacher, Doris Steinemann, Eric Hahnen, Karin Kast, Norbert Arnold, Raymonda Varon-Mateeva, Dorothea Wand, Andrew K. Godwin, D. Gareth Evans, Debra Frost, Jo Perkins, Julian Adlard, Louise Izatt, Radka Platte, Ros Eeles, Steve Ellis, Ute Hamann, Judy Garber, Florentia Fostira, George Fountzilas, Barbara Pasini, Giuseppe Giannini, Piera Rizzolo, Antonio Russo, Laura Cortesi, Laura Papi, Liliana Varesco, Domenico Palli, Ines Zanna, Antonella Savarese, Paolo Radice, Siranoush Manoukian, Bernard Peissel, Monica Barile, Bernardo Bonanni, Alessandra Viel, Valeria Pensotti, Stefania Tommasi, Paolo Peterlongo, Jeffrey N. Weitzel, Ana Osorio, Javier Benitez, Lesley McGuffog, Sue Healey, Anne Marie Gerdes, Bent Ejlertsen, Thomas V.O. Hansen, Linda Steele, Yuan Chun Ding, Nadine Tung, Ramunas Janavicius, David E. Goldgar, Saundra S. Buys, Mary B. Daly, Anita Bane, Mary Beth Terry, Esther M. John, Melissa Southey, Douglas F. Easton, Georgia Chenevix-Trench, Antonis C. Antoniou, Laura Ottini

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

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.

Original language	English (US)
Article number	15
Journal	Breast Cancer Research
Volume	18
Issue number	1
DOIs	https://doi.org/10.1186/s13058-016-0671-y
State	Published - Feb 9 2016

Keywords

BRCA1/2
Genotype-phenotype correlations
Histologic grade
Male breast cancer
Pathology

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1186/s13058-016-0671-y

Cite this

Silvestri, V., Barrowdale, D., Mulligan, A. M., Neuhausen, S. L., Fox, S., Karlan, B. Y., Mitchell, G., James, P., Thull, D. L., Zorn, K. K., Carter, N. J., Nathanson, K. L., Domchek, S. M., Rebbeck, T. R., Ramus, S. J., Nussbaum, R. L., Olopade, O. I., Rantala, J., Yoon, S. Y., ... Ottini, L. (2016). Male breast cancer in BRCA1 and BRCA2 mutation carriers: Pathology data from the Consortium of Investigators of Modifiers of BRCA1/2. Breast Cancer Research, 18(1), Article 15. https://doi.org/10.1186/s13058-016-0671-y

Silvestri, V, Barrowdale, D, Mulligan, AM, Neuhausen, SL, Fox, S, Karlan, BY, Mitchell, G, James, P, Thull, DL, Zorn, KK, Carter, NJ, Nathanson, KL, Domchek, SM, Rebbeck, TR, Ramus, SJ, Nussbaum, RL, Olopade, OI, Rantala, J, Yoon, SY, Caligo, MA, Spugnesi, L, Bojesen, A, Pedersen, IS, Thomassen, M, Jensen, UB, Toland, AE, Senter, L, Andrulis, IL, Glendon, G, Hulick, PJ, Imyanitov, EN, Greene, MH, Mai, PL, Singer, CF, Rappaport-Fuerhauser, C, Kramer, G, Vijai, J, Offit, K, Robson, M, Lincoln, A, Jacobs, L, Machackova, E, Foretova, L, Navratilova, M, Vasickova, P, Couch, FJ, Hallberg, E, Ruddy, KJ, Sharma, P, Kim, SW, Teixeira, MR, Pinto, P, Montagna, M, Matricardi, L, Arason, A, Johannsson, OT, Barkardottir, RB, Jakubowska, A, Lubinski, J, Izquierdo, A, Pujana, MA, Balmaña, J, Diez, O, Ivady, G, Papp, J, Olah, E, Kwong, A, Nevanlinna, H, Aittomäki, K, Perez Segura, P, Caldes, T, Van Maerken, T, Poppe, B, Claes, KBM, Isaacs, C, Elan, C, Lasset, C, Stoppa-Lyonnet, D, Barjhoux, L, Belotti, M, Meindl, A, Gehrig, A, Sutter, C, Engel, C, Niederacher, D, Steinemann, D, Hahnen, E, Kast, K, Arnold, N, Varon-Mateeva, R, Wand, D, Godwin, AK, Evans, DG, Frost, D, Perkins, J, Adlard, J, Izatt, L, Platte, R, Eeles, R, Ellis, S, Hamann, U, Garber, J, Fostira, F, Fountzilas, G, Pasini, B, Giannini, G, Rizzolo, P, Russo, A, Cortesi, L, Papi, L, Varesco, L, Palli, D, Zanna, I, Savarese, A, Radice, P, Manoukian, S, Peissel, B, Barile, M, Bonanni, B, Viel, A, Pensotti, V, Tommasi, S, Peterlongo, P, Weitzel, JN, Osorio, A, Benitez, J, McGuffog, L, Healey, S, Gerdes, AM, Ejlertsen, B, Hansen, TVO, Steele, L, Ding, YC, Tung, N, Janavicius, R, Goldgar, DE, Buys, SS, Daly, MB, Bane, A, Terry, MB, John, EM, Southey, M, Easton, DF, Chenevix-Trench, G, Antoniou, AC & Ottini, L 2016, 'Male breast cancer in BRCA1 and BRCA2 mutation carriers: Pathology data from the Consortium of Investigators of Modifiers of BRCA1/2', Breast Cancer Research, vol. 18, no. 1, 15. https://doi.org/10.1186/s13058-016-0671-y

@article{24a7652113174f8f865bc26b51b126f5,

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.",

keywords = "BRCA1/2, Genotype-phenotype correlations, Histologic grade, Male breast cancer, Pathology",

author = "Valentina Silvestri and Daniel Barrowdale and Mulligan, {Anna Marie} and Neuhausen, {Susan L.} and Stephen Fox and Karlan, {Beth Y.} and Gillian Mitchell and Paul James and Thull, {Darcy L.} and Zorn, {Kristin K.} and Carter, {Natalie J.} and Nathanson, {Katherine L.} and Domchek, {Susan M.} and Rebbeck, {Timothy R.} and Ramus, {Susan J.} and Nussbaum, {Robert L.} and Olopade, {Olufunmilayo I.} and Johanna Rantala and Yoon, {Sook Yee} and Caligo, {Maria A.} and Laura Spugnesi and Anders Bojesen and Pedersen, {Inge Sokilde} and Mads Thomassen and Jensen, {Uffe Birk} and Toland, {Amanda Ewart} and Leigha Senter and Andrulis, {Irene L.} and Gord Glendon and Hulick, {Peter J.} and Imyanitov, {Evgeny N.} and Greene, {Mark H.} and Mai, {Phuong L.} and Singer, {Christian F.} and Christine Rappaport-Fuerhauser and Gero Kramer and Joseph Vijai and Kenneth Offit and Mark Robson and Anne Lincoln and Lauren Jacobs and Eva Machackova and Lenka Foretova and Marie Navratilova and Petra Vasickova and Couch, {Fergus J.} and Emily Hallberg and Ruddy, {Kathryn J.} and Priyanka Sharma and Kim, {Sung Won} and Teixeira, {Manuel R.} and Pedro Pinto and Marco Montagna and Laura Matricardi and Adalgeir Arason and Johannsson, {Oskar Th} and Barkardottir, {Rosa B.} and Anna Jakubowska and Jan Lubinski and Angel Izquierdo and Pujana, {Miguel Angel} and Judith Balma{\~n}a and Orland Diez and Gabriella Ivady and Janos Papp and Edith Olah and Ava Kwong and Heli Nevanlinna and Kristiina Aittom{\"a}ki and {Perez Segura}, Pedro and Trinidad Caldes and {Van Maerken}, Tom and Bruce Poppe and Claes, {Kathleen B.M.} and Claudine Isaacs and Camille Elan and Christine Lasset and Dominique Stoppa-Lyonnet and Laure Barjhoux and Muriel Belotti and Alfons Meindl and Andrea Gehrig and Christian Sutter and Christoph Engel and Dieter Niederacher and Doris Steinemann and Eric Hahnen and Karin Kast and Norbert Arnold and Raymonda Varon-Mateeva and Dorothea Wand and Godwin, {Andrew K.} and Evans, {D. Gareth} and Debra Frost and Jo Perkins and Julian Adlard and Louise Izatt and Radka Platte and Ros Eeles and Steve Ellis and Ute Hamann and Judy Garber and Florentia Fostira and George Fountzilas and Barbara Pasini and Giuseppe Giannini and Piera Rizzolo and Antonio Russo and Laura Cortesi and Laura Papi and Liliana Varesco and Domenico Palli and Ines Zanna and Antonella Savarese and Paolo Radice and Siranoush Manoukian and Bernard Peissel and Monica Barile and Bernardo Bonanni and Alessandra Viel and Valeria Pensotti and Stefania Tommasi and Paolo Peterlongo and Weitzel, {Jeffrey N.} and Ana Osorio and Javier Benitez and Lesley McGuffog and Sue Healey and Gerdes, {Anne Marie} and Bent Ejlertsen and Hansen, {Thomas V.O.} and Linda Steele and Ding, {Yuan Chun} and Nadine Tung and Ramunas Janavicius and Goldgar, {David E.} and Buys, {Saundra S.} and Daly, {Mary B.} and Anita Bane and Terry, {Mary Beth} and John, {Esther M.} and Melissa Southey and Easton, {Douglas F.} and Georgia Chenevix-Trench and Antoniou, {Antonis C.} and Laura Ottini",

note = "Publisher Copyright: {\textcopyright} 2016 Silvestri et al.",

year = "2016",

month = feb,

day = "9",

doi = "10.1186/s13058-016-0671-y",

language = "English (US)",

volume = "18",

journal = "Breast Cancer Research",

issn = "1465-5411",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - Male breast cancer in BRCA1 and BRCA2 mutation carriers

T2 - Pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

AU - Silvestri, Valentina

AU - Barrowdale, Daniel

AU - Mulligan, Anna Marie

AU - Neuhausen, Susan L.

AU - Fox, Stephen

AU - Karlan, Beth Y.

AU - Mitchell, Gillian

AU - James, Paul

AU - Thull, Darcy L.

AU - Zorn, Kristin K.

AU - Carter, Natalie J.

AU - Nathanson, Katherine L.

AU - Domchek, Susan M.

AU - Rebbeck, Timothy R.

AU - Ramus, Susan J.

AU - Nussbaum, Robert L.

AU - Olopade, Olufunmilayo I.

AU - Rantala, Johanna

AU - Yoon, Sook Yee

AU - Caligo, Maria A.

AU - Spugnesi, Laura

AU - Bojesen, Anders

AU - Pedersen, Inge Sokilde

AU - Thomassen, Mads

AU - Jensen, Uffe Birk

AU - Toland, Amanda Ewart

AU - Senter, Leigha

AU - Andrulis, Irene L.

AU - Glendon, Gord

AU - Hulick, Peter J.

AU - Imyanitov, Evgeny N.

AU - Greene, Mark H.

AU - Mai, Phuong L.

AU - Singer, Christian F.

AU - Rappaport-Fuerhauser, Christine

AU - Kramer, Gero

AU - Vijai, Joseph

AU - Offit, Kenneth

AU - Robson, Mark

AU - Lincoln, Anne

AU - Jacobs, Lauren

AU - Machackova, Eva

AU - Foretova, Lenka

AU - Navratilova, Marie

AU - Vasickova, Petra

AU - Couch, Fergus J.

AU - Hallberg, Emily

AU - Ruddy, Kathryn J.

AU - Sharma, Priyanka

AU - Kim, Sung Won

AU - Teixeira, Manuel R.

AU - Pinto, Pedro

AU - Montagna, Marco

AU - Matricardi, Laura

AU - Arason, Adalgeir

AU - Johannsson, Oskar Th

AU - Barkardottir, Rosa B.

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Izquierdo, Angel

AU - Pujana, Miguel Angel

AU - Balmaña, Judith

AU - Diez, Orland

AU - Ivady, Gabriella

AU - Papp, Janos

AU - Olah, Edith

AU - Kwong, Ava

AU - Nevanlinna, Heli

AU - Aittomäki, Kristiina

AU - Perez Segura, Pedro

AU - Caldes, Trinidad

AU - Van Maerken, Tom

AU - Poppe, Bruce

AU - Claes, Kathleen B.M.

AU - Isaacs, Claudine

AU - Elan, Camille

AU - Lasset, Christine

AU - Stoppa-Lyonnet, Dominique

AU - Barjhoux, Laure

AU - Belotti, Muriel

AU - Meindl, Alfons

AU - Gehrig, Andrea

AU - Sutter, Christian

AU - Engel, Christoph

AU - Niederacher, Dieter

AU - Steinemann, Doris

AU - Hahnen, Eric

AU - Kast, Karin

AU - Arnold, Norbert

AU - Varon-Mateeva, Raymonda

AU - Wand, Dorothea

AU - Godwin, Andrew K.

AU - Evans, D. Gareth

AU - Frost, Debra

AU - Perkins, Jo

AU - Adlard, Julian

AU - Izatt, Louise

AU - Platte, Radka

AU - Eeles, Ros

AU - Ellis, Steve

AU - Hamann, Ute

AU - Garber, Judy

AU - Fostira, Florentia

AU - Fountzilas, George

AU - Pasini, Barbara

AU - Giannini, Giuseppe

AU - Rizzolo, Piera

AU - Russo, Antonio

AU - Cortesi, Laura

AU - Papi, Laura

AU - Varesco, Liliana

AU - Palli, Domenico

AU - Zanna, Ines

AU - Savarese, Antonella

AU - Radice, Paolo

AU - Manoukian, Siranoush

AU - Peissel, Bernard

AU - Barile, Monica

AU - Bonanni, Bernardo

AU - Viel, Alessandra

AU - Pensotti, Valeria

AU - Tommasi, Stefania

AU - Peterlongo, Paolo

AU - Weitzel, Jeffrey N.

AU - Osorio, Ana

AU - Benitez, Javier

AU - McGuffog, Lesley

AU - Healey, Sue

AU - Gerdes, Anne Marie

AU - Ejlertsen, Bent

AU - Hansen, Thomas V.O.

AU - Steele, Linda

AU - Ding, Yuan Chun

AU - Tung, Nadine

AU - Janavicius, Ramunas

AU - Goldgar, David E.

AU - Buys, Saundra S.

AU - Daly, Mary B.

AU - Bane, Anita

AU - Terry, Mary Beth

AU - John, Esther M.

AU - Southey, Melissa

AU - Easton, Douglas F.

AU - Chenevix-Trench, Georgia

AU - Antoniou, Antonis C.

AU - Ottini, Laura

PY - 2016/2/9

Y1 - 2016/2/9

N2 - 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.

AB - 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.

KW - BRCA1/2

KW - Genotype-phenotype correlations

KW - Histologic grade

KW - Male breast cancer

KW - Pathology

UR - http://www.scopus.com/inward/record.url?scp=84958120242&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958120242&partnerID=8YFLogxK

U2 - 10.1186/s13058-016-0671-y

DO - 10.1186/s13058-016-0671-y

M3 - Article

C2 - 26857456

AN - SCOPUS:84958120242

SN - 1465-5411

VL - 18

JO - Breast Cancer Research

JF - Breast Cancer Research

IS - 1

M1 - 15

ER -

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

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