title: Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade.
abstract: OBJECTIVE
  A number of microarray studies have reported distinct molecular profiles of breast cancers (BC), such as basal-like, ErbB2-like, and two to three luminal-like subtypes. These were associated with different clinical outcomes. However, although the basal and the ErbB2 subtypes are repeatedly recognized, identification of estrogen receptor (ER) -positive subtypes has been inconsistent. Therefore, refinement of their molecular definition is needed.
  
  
  METHODS
  We have previously reported a gene expression grade index (GGI), which defines histologic grade based on gene expression profiles. Using this algorithm, we assigned ER-positive BC to either high-or low-genomic grade subgroups and compared these with previously reported ER-positive molecular classifications. As further validation, we classified 666 ER-positive samples into subtypes and assessed their clinical outcome.
  
  
  RESULTS
  Two ER-positive molecular subgroups (high and low genomic grade) could be defined using the GGI. Despite tracking a single biologic pathway, these were highly comparable to the previously described luminal A and B classification and significantly correlated to the risk groups produced using the 21-gene recurrence score. The two subtypes were associated with statistically distinct clinical outcome in both systemically untreated and tamoxifen-treated populations.
  
  
  CONCLUSIONS
  The use of genomic grade can identify two clinically distinct ER-positive molecular subtypes in a simple and highly reproducible manner across multiple data sets. This study emphasizes the important role of proliferation-related genes in predicting prognosis in ER-positive BC.
authors.affiliation: Jules Bordet Institute; Machine Learning Group, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Sherene
authors.initials: S
authors.lastname: Loi
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haibe-Kains
authors.forename: Christine
authors.initials: C
authors.lastname: Desmedt
authors.forename: Françoise
authors.initials: F
authors.lastname: Lallemand
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tutt
authors.forename: Cheryl
authors.initials: C
authors.lastname: Gillet
authors.forename: Paul
authors.initials: P
authors.lastname: Ellis
authors.forename: Adrian
authors.initials: A
authors.lastname: Harris
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
authors.forename: Jan G M
authors.initials: JG
authors.lastname: Klijn
authors.forename: Denis
authors.initials: D
authors.lastname: Larsimont
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
authors.forename: Gianluca
authors.initials: G
authors.lastname: Bontempi
authors.forename: Mauro
authors.initials: M
authors.lastname: Delorenzi
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Piccart
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
mesh_terms: D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015999:Multivariate Analysis; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis*; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D011960:Receptors, Estrogen; D013629:Tamoxifen