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

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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 ERα, ERβ1, -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 phenotype 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 ERβ1/2 clusters. A striking feature was the occurrence of ERα on distinct clusters between genders. In female breast cancer, ERα clustered with PR and its isoforms; in male breast cancer, ERα clustered with ERβ 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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Acknowledgments

Thanks to the Tayside Tissue Bank for kindly providing some of the MBC cases. This study was supported by the Breast Cancer Campaign (UK Charity no. 05074725).

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Authors and Affiliations

  1. St James’s Institute of Oncology, St James’s University Hospital, Leeds, UK

    Abeer M. Shaaban, Rebecca A. Brannan, Georgina Reall, Eldo T. Verghese & Andrew M. Hanby

  2. Nottingham Trent University, Nottingham, UK

    Graham R. Ball

  3. Leeds Institute of Molecular Medicine, Wellcome Trust Brenner Building, University of Leeds, Leeds, LS9 7TF, UK

    Rebecca A. Brannan, Helen Honarpisheh, Loaie Maraqa, Steven Pollock, Eldo T. Verghese, Andrew M. Hanby & Valerie Speirs

  4. Bacs-Kiskun County Teaching Hospital, Nyiri ut 38, Kecskemet, 6000, Hungary

    Gabor Cserni

  5. Regina Elena Cancer Institute, Rome, Italy

    Anna Di Benedetto & Marcella Mottolese

  6. Calderdale Hospital, Halifax, UK

    Jo Dent

  7. Surrey & Sussex NHS Trust, Redhill, UK

    Laura Fulford

  8. University of Dundee/NHS Tayside, Dundee, UK

    Lee Jordan & Philip R. Quinlan

  9. Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, London, UK

    J. Louise Jones

  10. University of Saskatchewan, Saskatoon, Canada

    Rani Kanthan

  11. Poznan University of Medical Sciences, Poznan, Poland

    Maria Litwiniuk

  12. Addenbrookes Hospital, Cambridge, UK

    Elena Provenzano

  13. Imperial College, London, UK

    Sami Shousha

  14. University Hospital of North Staffordshire, Stoke-on Trent, UK

    Mark Stephens

  15. University of Leicester, Leicester, UK

    Rosemary A. Walker

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  1. Abeer M. Shaaban
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Shaaban, A.M., Ball, G.R., Brannan, R.A. et al. A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences. Breast Cancer Res Treat 133, 949–958 (2012). https://doi.org/10.1007/s10549-011-1856-9

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