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 StephensEldo T Verghese, Rosemary A Walker, Andrew M Hanby, Valerie Speirs

Research output: Contribution to journalArticle

71 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 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.

Original languageEnglish
Pages (from-to)949-58
Number of pages10
JournalBreast Cancer Research and Treatment
Volume133
Issue number3
Early online date18 Nov 2011
DOIs
Publication statusPublished - Jun 2012

Fingerprint

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

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Breast Neoplasms
  • Breast Neoplasms, Male
  • Cluster Analysis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Receptor, ErbB-2
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Sex Factors
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

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, 06.2012, p. 949-58.

Research output: Contribution to journalArticle

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. 949-58. https://doi.org/10.1007/s10549-011-1856-9
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. 949-58.
@article{de6cb021f98d409c8fc22fa34134d8ec,
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 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.",
keywords = "Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Breast Neoplasms, Breast Neoplasms, Male, Cluster Analysis, Female, Humans, Male, Middle Aged, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Sex Factors, Journal Article, Research Support, Non-U.S. Gov't",
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",
note = "Acknowledgements 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).",
year = "2012",
month = "6",
doi = "10.1007/s10549-011-1856-9",
language = "English",
volume = "133",
pages = "949--58",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "3",

}

TY - JOUR

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 - Acknowledgements 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).

PY - 2012/6

Y1 - 2012/6

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 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.

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 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers, Tumor

KW - Breast Neoplasms

KW - Breast Neoplasms, Male

KW - Cluster Analysis

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Receptor, ErbB-2

KW - Receptors, Estrogen

KW - Receptors, Progesterone

KW - Sex Factors

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1007/s10549-011-1856-9

DO - 10.1007/s10549-011-1856-9

M3 - Article

C2 - 22094935

VL - 133

SP - 949

EP - 958

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 3

ER -