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.
authors.affiliation: St James's Institute of Oncology, St James's University Hospital, Leeds, UK.
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Shaaban
authors.forename: Graham R
authors.initials: GR
authors.lastname: Ball
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Brannan
authors.forename: Gabor
authors.initials: G
authors.lastname: Cserni
authors.forename: Anna
authors.initials: A
authors.lastname: Di Benedetto
authors.forename: Jo
authors.initials: J
authors.lastname: Dent
authors.forename: Laura
authors.initials: L
authors.lastname: Fulford
authors.forename: Helen
authors.initials: H
authors.lastname: Honarpisheh
authors.forename: Lee
authors.initials: L
authors.lastname: Jordan
authors.forename: J Louise
authors.initials: JL
authors.lastname: Jones
authors.forename: Rani
authors.initials: R
authors.lastname: Kanthan
authors.forename: Loaie
authors.initials: L
authors.lastname: Maraqa
authors.forename: Maria
authors.initials: M
authors.lastname: Litwiniuk
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
authors.forename: Steven
authors.initials: S
authors.lastname: Pollock
authors.forename: Elena
authors.initials: E
authors.lastname: Provenzano
authors.forename: Philip R
authors.initials: PR
authors.lastname: Quinlan
authors.forename: Georgina
authors.initials: G
authors.lastname: Reall
authors.forename: Sami
authors.initials: S
authors.lastname: Shousha
authors.forename: Mark
authors.initials: M
authors.lastname: Stephens
authors.forename: Eldo T
authors.initials: ET
authors.lastname: Verghese
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Walker
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hanby
authors.forename: Valerie
authors.initials: V
authors.lastname: Speirs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality*; D018567:Breast Neoplasms, Male / Q000378:metabolism* / Q000401:mortality*; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012737:Sex Factors
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone