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 - http://www.scopus.com/inward/record.url?scp=84863728437&partnerID=8YFLogxK
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 -