A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences

Abeer M. Shaaban, Graham R. Ball, Rebecca A. Brannan, Gabor Cserni, Anna Di Benedetto, Jo Dent, Laura Fulford, Helen Honarpisheh, Lee Jordan, J. Louise Jones, Rani Kanthan, Loaie Maraqa, Maria Litwiniuk, Marcella Mottolese, Steven Pollock, Elena Provenzano, Philip R. Quinlan, Georgina Reall, Sami Shousha, Mark Stephens & 4 others Eldo T. Verghese, Rosemary A. Walker, Andrew M. Hanby, Valerie Speirs

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    66 Citations (Scopus)

    Abstract

    Male breast cancer remains understudied despite evidence of rising incidence. Using a co-ordinated multi-centre approach, we present the first large scale biomarker study to define and compare hormone receptor profiles and survival between male and female invasive breast cancer. We defined and compared hormone receptor profiles and survival between 251 male and 263 female breast cancers matched for grade, age, and lymph node status. Tissue microarrays were immunostained for ERa, ERß1, -2, -5, PR, PRA, PRB and AR, augmented by HER2, CK5/6, 14, 18 and 19 to assist typing. Hierarchical clustering determined differential nature of influences between genders. Luminal A was the most common phe-notype in both sexes. Luminal B and HER2 were not seen in males. Basal phenotype was infrequent in both. No differences in overall survival at 5 or 10 years were observed between genders. Notably, AR-positive luminal A male breast cancer had improved overall survival over female breast cancer at 5 (P = 0.01, HR = 0.39, 95% CI = 0.26-0.87) but not 10 years (P = 0.29, HR = 0.75, 95% CI = 0.46-1.26) and both 5 (P = 0.04, HR = 0.37, 95% CI = 0.07-0.97) and 10 years (P = 0.04, HR = 0.43, 95% CI = 0.12-0.97) in the unselected group. Hierarchical clustering revealed common clusters between genders including total PR-PRA-PRB and ERß1/2 clusters. A striking feature was the occurrence of ERa on distinct clusters between genders. In female breast cancer, ERa clustered with PR and its isoforms; in male breast cancer, ERa clustered with ERß isoforms and AR. Our data supports the hypothesis that breast cancer is biologically different in males and females suggesting implications for clinical management. With the incidence of male breast cancer increasing this provides impetus for further study.
    Original languageEnglish
    Pages (from-to)949-958
    Number of pages10
    JournalBreast Cancer Research and Treatment
    Volume133
    Issue number3
    DOIs
    Publication statusPublished - 2012

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    Male Breast Neoplasms
    Biomarkers
    Breast Neoplasms
    Cluster Analysis
    Protein Isoforms
    Hormones
    Incidence
    Lymph Nodes
    Phenotype

    Cite this

    Shaaban, Abeer M. ; Ball, Graham R. ; Brannan, Rebecca A. ; Cserni, Gabor ; Di Benedetto, Anna ; Dent, Jo ; Fulford, Laura ; Honarpisheh, Helen ; Jordan, Lee ; Jones, J. Louise ; Kanthan, Rani ; Maraqa, Loaie ; Litwiniuk, Maria ; Mottolese, Marcella ; Pollock, Steven ; Provenzano, Elena ; Quinlan, Philip R. ; Reall, Georgina ; Shousha, Sami ; Stephens, Mark ; Verghese, Eldo T. ; Walker, Rosemary A. ; Hanby, Andrew M. ; Speirs, Valerie. / A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences. In: Breast Cancer Research and Treatment. 2012 ; Vol. 133, No. 3. pp. 949-958.
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    title = "A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences",
    abstract = "Male breast cancer remains understudied despite evidence of rising incidence. Using a co-ordinated multi-centre approach, we present the first large scale biomarker study to define and compare hormone receptor profiles and survival between male and female invasive breast cancer. We defined and compared hormone receptor profiles and survival between 251 male and 263 female breast cancers matched for grade, age, and lymph node status. Tissue microarrays were immunostained for ERa, ER{\ss}1, -2, -5, PR, PRA, PRB and AR, augmented by HER2, CK5/6, 14, 18 and 19 to assist typing. Hierarchical clustering determined differential nature of influences between genders. Luminal A was the most common phe-notype in both sexes. Luminal B and HER2 were not seen in males. Basal phenotype was infrequent in both. No differences in overall survival at 5 or 10 years were observed between genders. Notably, AR-positive luminal A male breast cancer had improved overall survival over female breast cancer at 5 (P = 0.01, HR = 0.39, 95{\%} CI = 0.26-0.87) but not 10 years (P = 0.29, HR = 0.75, 95{\%} CI = 0.46-1.26) and both 5 (P = 0.04, HR = 0.37, 95{\%} CI = 0.07-0.97) and 10 years (P = 0.04, HR = 0.43, 95{\%} CI = 0.12-0.97) in the unselected group. Hierarchical clustering revealed common clusters between genders including total PR-PRA-PRB and ER{\ss}1/2 clusters. A striking feature was the occurrence of ERa on distinct clusters between genders. In female breast cancer, ERa clustered with PR and its isoforms; in male breast cancer, ERa clustered with ER{\ss} isoforms and AR. Our data supports the hypothesis that breast cancer is biologically different in males and females suggesting implications for clinical management. With the incidence of male breast cancer increasing this provides impetus for further study.",
    author = "Shaaban, {Abeer M.} and Ball, {Graham R.} and Brannan, {Rebecca A.} and Gabor Cserni and {Di Benedetto}, Anna and Jo Dent and Laura Fulford and Helen Honarpisheh and Lee Jordan and Jones, {J. Louise} and Rani Kanthan and Loaie Maraqa and Maria Litwiniuk and Marcella Mottolese and Steven Pollock and Elena Provenzano and Quinlan, {Philip R.} and Georgina Reall and Sami Shousha and Mark Stephens and Verghese, {Eldo T.} and Walker, {Rosemary A.} and Hanby, {Andrew M.} and Valerie Speirs",
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    Shaaban, AM, Ball, GR, Brannan, RA, Cserni, G, Di Benedetto, A, Dent, J, Fulford, L, Honarpisheh, H, Jordan, L, Jones, JL, Kanthan, R, Maraqa, L, Litwiniuk, M, Mottolese, M, Pollock, S, Provenzano, E, Quinlan, PR, Reall, G, Shousha, S, Stephens, M, Verghese, ET, Walker, RA, Hanby, AM & Speirs, V 2012, 'A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences', Breast Cancer Research and Treatment, vol. 133, no. 3, pp. 949-958. https://doi.org/10.1007/s10549-011-1856-9

    A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences. / Shaaban, Abeer M.; Ball, Graham R.; Brannan, Rebecca A.; Cserni, Gabor; Di Benedetto, Anna; Dent, Jo; Fulford, Laura; Honarpisheh, Helen; Jordan, Lee; Jones, J. Louise; Kanthan, Rani; Maraqa, Loaie; Litwiniuk, Maria; Mottolese, Marcella; Pollock, Steven; Provenzano, Elena; Quinlan, Philip R.; Reall, Georgina; Shousha, Sami; Stephens, Mark; Verghese, Eldo T.; Walker, Rosemary A.; Hanby, Andrew M.; Speirs, Valerie.

    In: Breast Cancer Research and Treatment, Vol. 133, No. 3, 2012, p. 949-958.

    Research output: Contribution to journalArticle

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    T1 - A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences

    AU - Shaaban, Abeer M.

    AU - Ball, Graham R.

    AU - Brannan, Rebecca A.

    AU - Cserni, Gabor

    AU - Di Benedetto, Anna

    AU - Dent, Jo

    AU - Fulford, Laura

    AU - Honarpisheh, Helen

    AU - Jordan, Lee

    AU - Jones, J. Louise

    AU - Kanthan, Rani

    AU - Maraqa, Loaie

    AU - Litwiniuk, Maria

    AU - Mottolese, Marcella

    AU - Pollock, Steven

    AU - Provenzano, Elena

    AU - Quinlan, Philip R.

    AU - Reall, Georgina

    AU - Shousha, Sami

    AU - Stephens, Mark

    AU - Verghese, Eldo T.

    AU - Walker, Rosemary A.

    AU - Hanby, Andrew M.

    AU - Speirs, Valerie

    N1 - Copyright 2012 Elsevier B.V., All rights reserved.

    PY - 2012

    Y1 - 2012

    N2 - Male breast cancer remains understudied despite evidence of rising incidence. Using a co-ordinated multi-centre approach, we present the first large scale biomarker study to define and compare hormone receptor profiles and survival between male and female invasive breast cancer. We defined and compared hormone receptor profiles and survival between 251 male and 263 female breast cancers matched for grade, age, and lymph node status. Tissue microarrays were immunostained for ERa, ERß1, -2, -5, PR, PRA, PRB and AR, augmented by HER2, CK5/6, 14, 18 and 19 to assist typing. Hierarchical clustering determined differential nature of influences between genders. Luminal A was the most common phe-notype in both sexes. Luminal B and HER2 were not seen in males. Basal phenotype was infrequent in both. No differences in overall survival at 5 or 10 years were observed between genders. Notably, AR-positive luminal A male breast cancer had improved overall survival over female breast cancer at 5 (P = 0.01, HR = 0.39, 95% CI = 0.26-0.87) but not 10 years (P = 0.29, HR = 0.75, 95% CI = 0.46-1.26) and both 5 (P = 0.04, HR = 0.37, 95% CI = 0.07-0.97) and 10 years (P = 0.04, HR = 0.43, 95% CI = 0.12-0.97) in the unselected group. Hierarchical clustering revealed common clusters between genders including total PR-PRA-PRB and ERß1/2 clusters. A striking feature was the occurrence of ERa on distinct clusters between genders. In female breast cancer, ERa clustered with PR and its isoforms; in male breast cancer, ERa clustered with ERß isoforms and AR. Our data supports the hypothesis that breast cancer is biologically different in males and females suggesting implications for clinical management. With the incidence of male breast cancer increasing this provides impetus for further study.

    AB - Male breast cancer remains understudied despite evidence of rising incidence. Using a co-ordinated multi-centre approach, we present the first large scale biomarker study to define and compare hormone receptor profiles and survival between male and female invasive breast cancer. We defined and compared hormone receptor profiles and survival between 251 male and 263 female breast cancers matched for grade, age, and lymph node status. Tissue microarrays were immunostained for ERa, ERß1, -2, -5, PR, PRA, PRB and AR, augmented by HER2, CK5/6, 14, 18 and 19 to assist typing. Hierarchical clustering determined differential nature of influences between genders. Luminal A was the most common phe-notype in both sexes. Luminal B and HER2 were not seen in males. Basal phenotype was infrequent in both. No differences in overall survival at 5 or 10 years were observed between genders. Notably, AR-positive luminal A male breast cancer had improved overall survival over female breast cancer at 5 (P = 0.01, HR = 0.39, 95% CI = 0.26-0.87) but not 10 years (P = 0.29, HR = 0.75, 95% CI = 0.46-1.26) and both 5 (P = 0.04, HR = 0.37, 95% CI = 0.07-0.97) and 10 years (P = 0.04, HR = 0.43, 95% CI = 0.12-0.97) in the unselected group. Hierarchical clustering revealed common clusters between genders including total PR-PRA-PRB and ERß1/2 clusters. A striking feature was the occurrence of ERa on distinct clusters between genders. In female breast cancer, ERa clustered with PR and its isoforms; in male breast cancer, ERa clustered with ERß isoforms and AR. Our data supports the hypothesis that breast cancer is biologically different in males and females suggesting implications for clinical management. With the incidence of male breast cancer increasing this provides impetus for further study.

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