title: Search for a gene expression signature of breast cancer local recurrence in young women.
abstract: OBJECTIVE
  A gene expression signature, predictive for local recurrence after breast-conserving treatment, has previously been identified from a series of 165 young patients with breast cancer. We evaluated this signature on both another platform and an independent series, compared its performance with other published gene-sets, and investigated the gene expression profile of a larger data set.
  
  
  METHODS
  Gene expression tumor profiles were obtained on 148 of the initial 165 Dutch patients and on an independent validation series of 195 French patients. Both unsupervised and supervised classifications were used to study the gene expression profile of the 343 breast cancers and to identify subgroups that differ for their risk of local recurrence.
  
  
  RESULTS
  The previous local recurrence signature was validated across platforms. However, when applied to the French patients, the signature did not reproduce its reported performance and did not better classify the patients than other published gene sets. Hierarchical clustering of all 343 breast cancers did not show any grouping reflecting local recurrence status. Genes related to proliferation were found differentially expressed between patients with or without local recurrence only in triple-negative tumors. Supervised classification revealed no significant gene set predictive for local recurrence or able to outperform classification based on clinical variables.
  
  
  CONCLUSIONS
  Although the previously identified local recurrence signature was robust on another platform, we were neither able to validate it on an independent data set, nor able to define a strong gene expression classifier for local recurrence using a larger data set. We conclude that there are no significant differences in gene expression pattern in tumors from patients with and without local recurrence after breast-conserving treatment.
authors.affiliation: Institut Curie, CNRS, Paris, France. Nicolas.Servant@curie.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Servant
authors.forename: Marc A
authors.initials: MA
authors.lastname: Bollet
authors.forename: Hans
authors.initials: H
authors.lastname: Halfwerk
authors.forename: Kevin
authors.initials: K
authors.lastname: Bleakley
authors.forename: Bas
authors.initials: B
authors.lastname: Kreike
authors.forename: Laurent
authors.initials: L
authors.lastname: Jacob
authors.forename: Daoud
authors.initials: D
authors.lastname: Sie
authors.forename: Ron M
authors.initials: RM
authors.lastname: Kerkhoven
authors.forename: Philippe
authors.initials: P
authors.lastname: Hupé
authors.forename: Rim
authors.initials: R
authors.lastname: Hadhri
authors.forename: Alain
authors.initials: A
authors.lastname: Fourquet
authors.forename: Harry
authors.initials: H
authors.lastname: Bartelink
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Barillot
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sigal-Zafrani
authors.forename: Marc J
authors.initials: MJ
authors.lastname: van de Vijver
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D011379:Prognosis; D012008:Recurrence; D054928:Validation Studies as Topic