title: Male breast cancer: Looking for better prognostic subgroups.
abstract: OBJECTIVE
  Male Breast Cancer (MBC) remains a poor understood disease. Prognostic factors are not well established and specific prognostic subgroups are warranted.
  
  
  METHODS
  Retrospectively revision of 111 cases treated in the same Cancer Center. Blinded-central pathological revision with immunohistochemical (IHQ) analysis for estrogen (ER), progesterone (PR) and androgen (AR) receptors, HER2, ki67 and p53 was done. Cox regression model was used for uni/multivariate survival analysis. Two classifications of Female Breast Cancer (FBC) subgroups (based in ER, PR, HER2, 2000 classification, and in ER, PR, HER2, ki67, 2013 classification) were used to achieve their prognostic value in MBC patients. Hierarchical clustering was performed to define subgroups based on the six-IHQ panel.
  
  
  RESULTS
  According to FBC classifications, the majority of tumors were luminal: A (89.2%; 60.0%) and B (7.2%; 35.8%). Triple negative phenotype was infrequent (2.7%; 3.2%) and HER2 enriched, non-luminal, was rare (≤1% in both). In multivariate analysis the poor prognostic factors were: size >2 cm (HR:1.8; 95%CI:1.0-3.4 years, p = 0.049), absence of ER (HR:4.9; 95%CI:1.7-14.3 years, p = 0.004) and presence of distant metastasis (HR:5.3; 95%CI:2.2-3.1 years, p < 0.001). FBC subtypes were independent prognostic factors (p = 0.009, p = 0.046), but when analyzed only luminal groups, prognosis did not differ regardless the classification used (p > 0.20). Clustering defined different subgroups, that have prognostic value in multivariate analysis (p = 0.005), with better survival in ER/PR+, AR-, HER2-and ki67/p53 low group (median: 11.5 years; 95%CI: 6.2-16.8 years) and worst in PR-group (median:4.5 years; 95%CI: 1.6-7.8 years).
  
  
  CONCLUSIONS
  FBC subtypes do not give the same prognostic information in MBC even in luminal groups. Two subgroups with distinct prognosis were identified in a common six-IHQ panel. Future studies must achieve their real prognostic value in these patients.
authors.affiliation: Department of Medical Oncology, Portuguese Institute of Oncology of Porto, Porto, Portugal. Electronic address: p_abreu@sapo.pt.
authors.forename: Miguel Henriques
authors.initials: MH
authors.lastname: Abreu
authors.affiliation: Department of Medical Oncology, Portuguese Institute of Oncology of Porto, Porto, Portugal.
authors.forename: Noémia
authors.initials: N
authors.lastname: Afonso
authors.affiliation: CISUC, Department of Informatics Engineering, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.
authors.forename: Pedro Henriques
authors.initials: PH
authors.lastname: Abreu
authors.affiliation: Department of Pathology, Portuguese Institute of Oncology of Porto, Porto, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Menezes
authors.affiliation: Department of Pathology, Portuguese Institute of Oncology of Porto, Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Lopes
authors.affiliation: Department of Pathology, Portuguese Institute of Oncology of Porto, Porto, Portugal; Department of Pathology and Molecular Immunology, Biomedical Sciences Institute of Abel Salazar, University of Porto, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.affiliation: Department of Medical Oncology, Portuguese Institute of Oncology of Porto, Porto, Portugal.
authors.forename: Deolinda
authors.initials: D
authors.lastname: Pereira
authors.affiliation: Department of Pathology and Molecular Immunology, Biomedical Sciences Institute of Abel Salazar, University of Porto, Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D018567:Breast Neoplasms, Male / Q000737:chemistry* / Q000145:classification* / Q000235:genetics; D016000:Cluster Analysis; D005500:Follow-Up Studies; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011944:Receptors, Androgen / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Male breast cancer; Prognostic subgroups; Survival