title: Gene expression profiles of inflammatory breast cancer: correlation with response to neoadjuvant chemotherapy and metastasis-free survival.
abstract: BACKGROUND
  Inflammatory breast cancer (IBC) is an aggressive disease. To date, no molecular feature reliably predicts either the response to chemotherapy (CT) or the survival. Using DNA microarrays, we searched for multigene predictors.
  
  
  METHODS
  The World IBC Consortium generated whole-genome expression profiles of 137 IBC and 252 non-IBC (nIBC) samples. We searched for transcriptional profiles associated with pathological complete response (pCR) to neoadjuvant anthracycline-based CT and distant metastasis-free survival (DMFS) in respective subsets of 87 and 106 informative IBC samples. Correlations were investigated with predictive and prognostic gene expression signatures published in nIBC (nIBC-GES). Supervised analyses tested genes and activation signatures of 19 biological pathways and 234 transcription factors.
  
  
  RESULTS
  Three of five tested prognostic nIBC-GES and the two tested predictive nIBC-GES discriminated between IBC with and without pCR, as well as two interferon activation signatures. We identified a 107-gene signature enriched for immunity-related genes that distinguished between responders and nonresponders in IBC. Its robustness was demonstrated by external validation in three independent sets including two IBC sets and one nIBC set, with independent significant predictive value in IBC and nIBC validation sets in multivariate analysis. We found no robust signature associated with DMFS in patients with IBC, and neither of the tested prognostic GES, nor the molecular subtypes were informative, whereas they were in our nIBC series (220 stage I-III informative samples).
  
  
  CONCLUSIONS
  Despite the relatively small sample size, we show that response to neoadjuvant CT in IBC is, as in nIBC, associated with immunity-related processes, suggesting that similar mechanisms responsible for pCR exist. Analysis of a larger IBC series is warranted regarding the correlation of gene expression profiles and DMFS.
authors.affiliation: Department of Molecular Oncology.
authors.forename: F
authors.initials: F
authors.lastname: Bertucci
authors.forename: N T
authors.initials: NT
authors.lastname: Ueno
authors.forename: P
authors.initials: P
authors.lastname: Finetti
authors.forename: P
authors.initials: P
authors.lastname: Vermeulen
authors.forename: A
authors.initials: A
authors.lastname: Lucci
authors.forename: F M
authors.initials: FM
authors.lastname: Robertson
authors.forename: M
authors.initials: M
authors.lastname: Marsan
authors.forename: T
authors.initials: T
authors.lastname: Iwamoto
authors.forename: S
authors.initials: S
authors.lastname: Krishnamurthy
authors.forename: H
authors.initials: H
authors.lastname: Masuda
authors.forename: P
authors.initials: P
authors.lastname: Van Dam
authors.forename: W A
authors.initials: WA
authors.lastname: Woodward
authors.forename: M
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: J M
authors.initials: JM
authors.lastname: Reuben
authors.forename: L
authors.initials: L
authors.lastname: Dirix
authors.forename: P
authors.initials: P
authors.lastname: Viens
authors.forename: W F
authors.initials: WF
authors.lastname: Symmans
authors.forename: D
authors.initials: D
authors.lastname: Birnbaum
authors.forename: S J
authors.initials: SJ
authors.lastname: Van Laere
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D047628:Estrogen Receptor alpha; D018719:Erb-b2 Receptor Tyrosine Kinases; C506487:ESR1 protein, human; C508053:ERBB2 protein, human
keywords: gene expression; inflammatory breast cancer; profiling; prognosis; response to chemotherapy