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; Anne-Marie Gerdes; kConFab Investigators

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, Anne-Marie Gerdes, kConFab Investigators

Department of Clinical Medicine

46 Citations (Scopus)

57 Downloads (Pure)

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
Article number	15
Journal	Breast Cancer Research (Online)
Volume	18
Number of pages	13
ISSN	1465-5411
DOIs	https://doi.org/10.1186/s13058-016-0671-y
Publication status	Published - 9 Feb 2016

Keywords

Adult
Aged
BRCA1 Protein
BRCA2 Protein
Breast Neoplasms
Breast Neoplasms, Male
Female
Genetic Predisposition to Disease
Humans
Male
Middle Aged
Mutation
Neoplasm Staging
Polymorphism, Single Nucleotide
Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2Final published version, 766 KBLicence: CC BY

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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., ... kConFab Investigators (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 (Online), 18, [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, S-Y, 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, Gerdes, A-M & kConFab Investigators 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 (Online), vol. 18, 15. https://doi.org/10.1186/s13058-016-0671-y

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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 = "Adult, Aged, BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, Breast Neoplasms, Male, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Mutation, Neoplasm Staging, Polymorphism, Single Nucleotide, Journal Article",

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 Sook-Yee Yoon 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 Anne-Marie Gerdes and {kConFab Investigators}",

year = "2016",

month = feb,

day = "9",

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

language = "English",

volume = "18",

journal = "Breast Cancer Research",

issn = "1465-5411",

publisher = "BioMed Central Ltd.",

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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 - Gerdes, Anne-Marie

AU - kConFab Investigators

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 - Adult

KW - Aged

KW - BRCA1 Protein

KW - BRCA2 Protein

KW - Breast Neoplasms

KW - Breast Neoplasms, Male

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Male

KW - Middle Aged

KW - Mutation

KW - Neoplasm Staging

KW - Polymorphism, Single Nucleotide

KW - Journal Article

U2 - 10.1186/s13058-016-0671-y

DO - 10.1186/s13058-016-0671-y

M3 - Journal article

C2 - 26857456

SN - 1465-5411

VL - 18

JO - Breast Cancer Research

JF - Breast Cancer Research

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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Keywords

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