title: Proposed new clinicopathological surrogate definitions of luminal A and luminal B (HER2-negative) intrinsic breast cancer subtypes.
abstract: BACKGROUND
  The St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013 recognized substantial progress in the pathological characterization of breast cancer subtypes. A useful surrogate definition was developed to distinguish luminal A-like breast cancer from luminal B-like disease based on a combination of estrogen receptor (ER), progesterone receptor (PgR) and Ki-67 status, without a requirement for molecular diagnostics. Differences depend upon the choice of the threshold value for Ki-67 and the requirement for substantial PgR positivity. We aimed to verify the suitability of the new surrogate definitions of luminal subtypes in terms of distant disease control in a large series of patients.
  
  
  METHODS
  We studied 9,415 women with a median follow-up of 8.1 years who (1) had ER-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer and (2) had undergone surgery at the European Institute of Oncology between 1994 and 2006. We evaluated distant disease-free survival of patients with "low" (<14%), "intermediate" (14% to 19%) or "high" (≥20%) Ki-67 positivity stratified by PgR expression (negative or low versus high). We calculated the cumulative incidence of distant events, considered competing events and performed multivariable analysis adjusted for pathologic tumor stage, pathologic node stage, tumor grade, peritumoral vascular invasion and menopausal status.
  
  
  RESULTS
  Lack of substantial PgR positivity was associated with poorer outcomes only for patients with an intermediate Ki-67 level (P<0.001). The 4,890 patients (51.9%) with low Ki-67 level (any PgR expression level) or with intermediate Ki-67 level but substantial PgR positivity had comparably good outcomes and thus may represent a most advantageous grouping of those with luminal A-like disease.
  
  
  CONCLUSIONS
  The updated pathological definition of intrinsic molecular subtypes may maximize the number of patients classified as having the luminal A-like intrinsic subtype of breast cancer and for whom the use of cytotoxic drugs could mostly be avoided.
authors.forename: Patrick
authors.initials: P
authors.lastname: Maisonneuve
authors.forename: Davide
authors.initials: D
authors.lastname: Disalvatore
authors.forename: Nicole
authors.initials: N
authors.lastname: Rotmensz
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curigliano
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
authors.forename: Silvia
authors.initials: S
authors.lastname: Dellapasqua
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Pruneri
authors.forename: Mauro G
authors.initials: MG
authors.lastname: Mastropasqua
authors.forename: Alberto
authors.initials: A
authors.lastname: Luini
authors.forename: Fabio
authors.initials: F
authors.lastname: Bassi
authors.forename: Gianmatteo
authors.initials: G
authors.lastname: Pagani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human