Characterisation of male breast cancer

a descriptive biomarker study from a large patient series

Matthew P Humphries, Sreekumar Sundara Rajan, Hedieh Honarpisheh, Gabor Cserni, Jo Dent, Laura Fulford, Lee B Jordan, J Louise Jones, Rani Kanthan, Maria Litwiniuk, Anna Di Benedetto, Marcella Mottolese, Elena Provenzano, Sami Shousha, Mark Stephens, Janina Kulka, Ian O Ellis, Akinwale N Titloye, Andrew M Hanby, Abeer M Shaaban & 1 others Valerie Speirs

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Abstract

Male breast cancer (MBC) is rare. We assembled 446 MBCs on tissue microarrays and assessed clinicopathological information, together with data from 15 published studies, totalling 1984 cases. By immunohistochemistry we investigated 14 biomarkers (ERα, ERβ1, ERβ2, ERβ5, PR, AR, Bcl-2, HER2, p53, E-cadherin, Ki67, survivin, prolactin, FOXA1) for survival impact. The main histological subtype in our cohort and combined analyses was ductal (81%, 83%), grade 2; (40%, 44%), respectively. Cases were predominantly ERα (84%, 82%) and PR positive (74%, 71%), respectively, with HER2 expression being infrequent (2%, 10%), respectively. In our cohort, advanced age (>67) was the strongest predictor of overall (OS) and disease free survival (DFS) (p = 0.00001; p = 0.01, respectively). Node positivity negatively impacted DFS (p = 0.04). FOXA1 p = 0.005) and AR p = 0.009) were both positively prognostic for DFS, remaining upon multivariate analysis. Network analysis showed ERα, AR and FOXA1 significantly correlated. In summary, the principle phenotype of MBC was luminal A, ductal, grade 2. In ERα+ MBC, only AR had prognostic significance, suggesting AR blockade could be employed therapeutically.

Original languageEnglish
Article number45293
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 28 Mar 2017

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Male Breast Neoplasms
Disease-Free Survival
Biomarkers
Cadherins
Prolactin
Cohort Studies
Multivariate Analysis
Immunohistochemistry
Phenotype
Survival

Keywords

  • Journal Article

Cite this

Humphries, M. P., Sundara Rajan, S., Honarpisheh, H., Cserni, G., Dent, J., Fulford, L., ... Speirs, V. (2017). Characterisation of male breast cancer: a descriptive biomarker study from a large patient series. Scientific Reports, 7, [45293]. https://doi.org/10.1038/srep45293

Characterisation of male breast cancer : a descriptive biomarker study from a large patient series. / Humphries, Matthew P; Sundara Rajan, Sreekumar; Honarpisheh, Hedieh; Cserni, Gabor; Dent, Jo; Fulford, Laura; Jordan, Lee B; Jones, J Louise; Kanthan, Rani; Litwiniuk, Maria; Di Benedetto, Anna; Mottolese, Marcella; Provenzano, Elena; Shousha, Sami; Stephens, Mark; Kulka, Janina; Ellis, Ian O; Titloye, Akinwale N; Hanby, Andrew M; Shaaban, Abeer M; Speirs, Valerie.

In: Scientific Reports, Vol. 7, 45293, 28.03.2017.

Research output: Contribution to journalArticle

Humphries, MP, Sundara Rajan, S, Honarpisheh, H, Cserni, G, Dent, J, Fulford, L, Jordan, LB, Jones, JL, Kanthan, R, Litwiniuk, M, Di Benedetto, A, Mottolese, M, Provenzano, E, Shousha, S, Stephens, M, Kulka, J, Ellis, IO, Titloye, AN, Hanby, AM, Shaaban, AM & Speirs, V 2017, 'Characterisation of male breast cancer: a descriptive biomarker study from a large patient series', Scientific Reports, vol. 7, 45293. https://doi.org/10.1038/srep45293
Humphries MP, Sundara Rajan S, Honarpisheh H, Cserni G, Dent J, Fulford L et al. Characterisation of male breast cancer: a descriptive biomarker study from a large patient series. Scientific Reports. 2017 Mar 28;7. 45293. https://doi.org/10.1038/srep45293
Humphries, Matthew P ; Sundara Rajan, Sreekumar ; Honarpisheh, Hedieh ; Cserni, Gabor ; Dent, Jo ; Fulford, Laura ; Jordan, Lee B ; Jones, J Louise ; Kanthan, Rani ; Litwiniuk, Maria ; Di Benedetto, Anna ; Mottolese, Marcella ; Provenzano, Elena ; Shousha, Sami ; Stephens, Mark ; Kulka, Janina ; Ellis, Ian O ; Titloye, Akinwale N ; Hanby, Andrew M ; Shaaban, Abeer M ; Speirs, Valerie. / Characterisation of male breast cancer : a descriptive biomarker study from a large patient series. In: Scientific Reports. 2017 ; Vol. 7.
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abstract = "Male breast cancer (MBC) is rare. We assembled 446 MBCs on tissue microarrays and assessed clinicopathological information, together with data from 15 published studies, totalling 1984 cases. By immunohistochemistry we investigated 14 biomarkers (ERα, ERβ1, ERβ2, ERβ5, PR, AR, Bcl-2, HER2, p53, E-cadherin, Ki67, survivin, prolactin, FOXA1) for survival impact. The main histological subtype in our cohort and combined analyses was ductal (81{\%}, 83{\%}), grade 2; (40{\%}, 44{\%}), respectively. Cases were predominantly ERα (84{\%}, 82{\%}) and PR positive (74{\%}, 71{\%}), respectively, with HER2 expression being infrequent (2{\%}, 10{\%}), respectively. In our cohort, advanced age (>67) was the strongest predictor of overall (OS) and disease free survival (DFS) (p = 0.00001; p = 0.01, respectively). Node positivity negatively impacted DFS (p = 0.04). FOXA1 p = 0.005) and AR p = 0.009) were both positively prognostic for DFS, remaining upon multivariate analysis. Network analysis showed ERα, AR and FOXA1 significantly correlated. In summary, the principle phenotype of MBC was luminal A, ductal, grade 2. In ERα+ MBC, only AR had prognostic significance, suggesting AR blockade could be employed therapeutically.",
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AU - Humphries, Matthew P

AU - Sundara Rajan, Sreekumar

AU - Honarpisheh, Hedieh

AU - Cserni, Gabor

AU - Dent, Jo

AU - Fulford, Laura

AU - Jordan, Lee B

AU - Jones, J Louise

AU - Kanthan, Rani

AU - Litwiniuk, Maria

AU - Di Benedetto, Anna

AU - Mottolese, Marcella

AU - Provenzano, Elena

AU - Shousha, Sami

AU - Stephens, Mark

AU - Kulka, Janina

AU - Ellis, Ian O

AU - Titloye, Akinwale N

AU - Hanby, Andrew M

AU - Shaaban, Abeer M

AU - Speirs, Valerie

N1 - This study was funded by Yorkshire Cancer Research (grant L378). Breast Cancer Now (formerly Breast Cancer Campaign, grant 2007 MayPR02) provided funding for the accrual and construction of TMAs. Thanks to Prof Rosemary Walker and Dr Margaret Jefferies for kindly donating tissue samples.

PY - 2017/3/28

Y1 - 2017/3/28

N2 - Male breast cancer (MBC) is rare. We assembled 446 MBCs on tissue microarrays and assessed clinicopathological information, together with data from 15 published studies, totalling 1984 cases. By immunohistochemistry we investigated 14 biomarkers (ERα, ERβ1, ERβ2, ERβ5, PR, AR, Bcl-2, HER2, p53, E-cadherin, Ki67, survivin, prolactin, FOXA1) for survival impact. The main histological subtype in our cohort and combined analyses was ductal (81%, 83%), grade 2; (40%, 44%), respectively. Cases were predominantly ERα (84%, 82%) and PR positive (74%, 71%), respectively, with HER2 expression being infrequent (2%, 10%), respectively. In our cohort, advanced age (>67) was the strongest predictor of overall (OS) and disease free survival (DFS) (p = 0.00001; p = 0.01, respectively). Node positivity negatively impacted DFS (p = 0.04). FOXA1 p = 0.005) and AR p = 0.009) were both positively prognostic for DFS, remaining upon multivariate analysis. Network analysis showed ERα, AR and FOXA1 significantly correlated. In summary, the principle phenotype of MBC was luminal A, ductal, grade 2. In ERα+ MBC, only AR had prognostic significance, suggesting AR blockade could be employed therapeutically.

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