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

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 - 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.

UR - https://www.scopus.com/pages/publications/84863728437

U2 - 10.1007/s10549-011-1856-9

DO - 10.1007/s10549-011-1856-9

M3 - Article

C2 - 22094935

AN - SCOPUS:84863728437

SN - 0167-6806

VL - 133

SP - 949

EP - 958

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

IS - 3

ER -