title: Predicting a local recurrence after breast-conserving therapy by gene expression profiling.
abstract: BACKGROUND
  To tailor local treatment in breast cancer patients there is a need for predicting ipsilateral recurrences after breast-conserving therapy. After adequate treatment (excision with free margins and radiotherapy), young age and incompletely excised extensive intraductal component are predictors for local recurrence, but many local recurrences can still not be predicted. Here we have used gene expression profiling by microarray analysis to identify gene expression profiles that can help to predict local recurrence in individual patients.
  
  
  METHODS
  By using previously established gene expression profiles with proven value in predicting metastasis-free and overall survival (wound-response signature, 70-gene prognosis profile and hypoxia-induced profile) and training towards an optimal prediction of local recurrences in a training series, we establish a classifier for local recurrence after breast-conserving therapy.
  
  
  RESULTS
  Validation of the different gene lists shows that the wound-response signature is able to separate patients with a high (29%) or low (5%) risk of a local recurrence at 10 years (sensitivity 87.5%, specificity 75%). In multivariable analysis the classifier is an independent predictor for local recurrence.
  
  
  CONCLUSIONS
  Our findings indicate that gene expression profiling can identify subgroups of patients at increased risk of developing a local recurrence after breast-conserving therapy.
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Dimitry S A
authors.initials: DS
authors.lastname: Nuyten
authors.forename: Bas
authors.initials: B
authors.lastname: Kreike
authors.forename: Augustinus A M
authors.initials: AA
authors.lastname: Hart
authors.forename: Jen-Tsan Ashley
authors.initials: JT
authors.lastname: Chi
authors.forename: Julie B
authors.initials: JB
authors.lastname: Sneddon
authors.forename: Lodewyk F A
authors.initials: LF
authors.lastname: Wessels
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Peterse
authors.forename: Harry
authors.initials: H
authors.lastname: Bartelink
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Brown
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
authors.forename: Marc J
authors.initials: MJ
authors.lastname: van de Vijver
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000628:therapy; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000628:therapy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011878:Radiotherapy