title: Characterisation of male breast cancer: a descriptive biomarker study from a large patient series.
abstract: Male breast cancer (MBC) is rare. We assembled 446 MBCs on tissue microarrays and assessed clinicopathological information, together with data from 15 published studies, totalling 1984 cases. By immunohistochemistry we investigated 14 biomarkers (ERα, ERβ1, ERβ2, ERβ5, PR, AR, Bcl-2, HER2, p53, E-cadherin, Ki67, survivin, prolactin, FOXA1) for survival impact. The main histological subtype in our cohort and combined analyses was ductal (81%, 83%), grade 2; (40%, 44%), respectively. Cases were predominantly ERα (84%, 82%) and PR positive (74%, 71%), respectively, with HER2 expression being infrequent (2%, 10%), respectively. In our cohort, advanced age (>67) was the strongest predictor of overall (OS) and disease free survival (DFS) (p = 0.00001; p = 0.01, respectively). Node positivity negatively impacted DFS (p = 0.04). FOXA1 p = 0.005) and AR p = 0.009) were both positively prognostic for DFS, remaining upon multivariate analysis. Network analysis showed ERα, AR and FOXA1 significantly correlated. In summary, the principle phenotype of MBC was luminal A, ductal, grade 2. In ERα+ MBC, only AR had prognostic significance, suggesting AR blockade could be employed therapeutically.
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, LS9 7TF, UK.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Humphries
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, LS9 7TF, UK.
authors.forename: Sreekumar
authors.initials: S
authors.lastname: Sundara Rajan
authors.affiliation: MD Anderson Cancer Centre, Houston, Texas, TX 77030, USA.
authors.forename: Hedieh
authors.initials: H
authors.lastname: Honarpisheh
authors.affiliation: Department of Pathology, Bács-Kiskun County Teaching Hospital, Nyiri ut 38, H-6000, Kecskemet, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Cserni
authors.affiliation: Calderdale Hospital, Halifax, HX3 0PW, UK.
authors.forename: Jo
authors.initials: J
authors.lastname: Dent
authors.affiliation: Surrey &Sussex NHS Trust, Redhill, Surrey, RH1 5RH, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Fulford
authors.affiliation: University of Dundee/NHS Tayside, Dundee, DD1 9SY, UK.
authors.forename: Lee B
authors.initials: LB
authors.lastname: Jordan
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK.
authors.forename: J Louise
authors.initials: JL
authors.lastname: Jones
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Saskatchewan, Royal University Hospital, Saskatoon, Saskatchewan S7N 0W8, Canada.
authors.forename: Rani
authors.initials: R
authors.lastname: Kanthan
authors.affiliation: Poznan University of Medical Sciences, Greater Poland Cancer Centre, Poznan, 02-004, Warsaw Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Litwiniuk
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute. Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Di Benedetto
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute. Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
authors.affiliation: Department of Histopathology, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Provenzano
authors.affiliation: Department of Histopathology, Imperial College Healthcare NHS Trust and Imperial College, Charing Cross Hospital, London W6 8RF, UK.
authors.forename: Sami
authors.initials: S
authors.lastname: Shousha
authors.affiliation: University Hospital of North Staffordshire, Stoke-on Trent, ST4 6QG, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Stephens
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Üllői út. 93, Budapest 1091, Hungary.
authors.forename: Janina
authors.initials: J
authors.lastname: Kulka
authors.affiliation: Faculty of Medicine &Health Sciences, Nottingham City Hospital. Nottingham, NG5 1PB, UK.
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.affiliation: School of Medical Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Akinwale N
authors.initials: AN
authors.lastname: Titloye
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, LS9 7TF, UK.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hanby
authors.affiliation: Department of Cellular Pathology, Queen Elizabeth Hospital Birmingham and University of Birmingham, Birmingham, B15 2TW, UK.
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Shaaban
authors.affiliation: Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, LS9 7TF, UK.
authors.forename: Valerie
authors.initials: V
authors.lastname: Speirs
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D018567:Breast Neoplasms, Male / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000378:metabolism; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D011944:Receptors, Androgen / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D011944:Receptors, Androgen