title: Molecular subtyping of male breast cancer using alternative definitions and its prognostic impact.
abstract: BACKGROUND
  Male breast cancer (MBC) is an uncommon disease and there is limited information on the prognostic impact of routinely used clinicopathological parameters.
  
  
  METHODS
  In a retrospective setting, we reviewed 197 MBC patients with accessible paraffin-embedded tumor tissue and clinicopathological data. Immunohistochemical (IHC) stainings were performed on tissue microarrays and histological grading on conventional slides. Cox proportional regression models were applied for uni- and multivariate analyses using breast cancer death as the event.
  
  
  RESULTS
  Estrogen receptor (ER) and progesterone receptor positivity were demonstrated in 93% and 77% of patients, respectively. Nottingham histologic grade (NHG) III was seen in 41% and HER2 positivity in 11%. Classification into molecular subtypes using IHC markers according to three alternative definitions revealed luminal A and luminal B in 81% vs. 11%; 48% vs. 44% and 41% vs. 42% of cases. Two cases of basal-like were identified, but no cases of HER2-like. Factors associated with an increased risk of breast cancer death were node positivity (HR 4.5; 95% CI 1.8-11.1), tumor size > 20 mm (HR 3.3; 95% CI 1.4-7.9) and ER negativity (HR 10.9; 95% CI 3.2-37.9). No difference in breast cancer death between the luminal subgroups was demonstrated, regardless of definition.
  
  
  CONCLUSIONS
  MBC tumors were more often of high grade, whereas HER2 overexpression was as frequent as in FBC. Lymph nodes, tumor size and ER status were independent predictors of breast cancer death. The prognostic impact of molecular subtyping in MBC seems to differ from that previously established in FBC.
authors.affiliation: Center for Clinical Research, Västmanland County Hospital, Västerås, Sweden. cecilia.nilsson@ltv.se
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nilsson
authors.forename: Ida
authors.initials: I
authors.lastname: Johansson
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ahlin
authors.forename: Sten
authors.initials: S
authors.lastname: Thorstenson
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Amini
authors.forename: Marit
authors.initials: M
authors.lastname: Holmqvist
authors.forename: Leif
authors.initials: L
authors.lastname: Bergkvist
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hedenfalk
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Fjällskog
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018567:Breast Neoplasms, Male / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012042:Registries; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human