title: Development and validation of a gene profile predicting benefit of postmastectomy radiotherapy in patients with high-risk breast cancer: a study of gene expression in the DBCG82bc cohort.
abstract: OBJECTIVE
  To identify genes predicting benefit of radiotherapy in patients with high-risk breast cancer treated with systemic therapy and randomized to receive or not receive postmastectomy radiotherapy (PMRT).
  
  
  METHODS
  The study was based on the Danish Breast Cancer Cooperative Group (DBCG82bc) cohort. Gene-expression analysis was performed in a training set of frozen tumor tissue from 191 patients. Genes were identified through the Lasso method with the endpoint being locoregional recurrence (LRR). A weighted gene-expression index (DBCG-RT profile) was calculated and transferred to quantitative real-time PCR (qRT-PCR) in corresponding formalin-fixed, paraffin-embedded (FFPE) samples, before validation in FFPE from 112 additional patients.
  
  
  RESULTS
  Seven genes were identified, and the derived DBCG-RT profile divided the 191 patients into "high LRR risk" and "low LRR risk" groups. PMRT significantly reduced risk of LRR in "high LRR risk" patients, whereas "low LRR risk" patients showed no additional reduction in LRR rate. Technical transfer of the DBCG-RT profile to FFPE/qRT-PCR was successful, and the predictive impact was successfully validated in another 112 patients.
  
  
  CONCLUSIONS
  A DBCG-RT gene profile was identified and validated, identifying patients with very low risk of LRR and no benefit from PMRT. The profile may provide a method to individualize treatment with PMRT.
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark. tramm@oncology.au.dk.
authors.forename: Trine
authors.initials: T
authors.lastname: Tramm
authors.affiliation: Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Hayat
authors.initials: H
authors.lastname: Mohammed
authors.affiliation: Department of Genetics, Institute of Cancer Research, Oslo University Hospital, Radiumhospitalet, Norway. K-G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Atlantis Medical University College, Oslo, Norway.
authors.forename: Simen
authors.initials: S
authors.lastname: Myhre
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Kyndi
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Alsner
authors.affiliation: Department of Genetics, Institute of Cancer Research, Oslo University Hospital, Radiumhospitalet, Norway. K-G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.affiliation: Department of Genetics, Institute of Cancer Research, Oslo University Hospital, Radiumhospitalet, Norway. K-G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Therese
authors.initials: T
authors.lastname: Sørlie
authors.affiliation: Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Arnoldo
authors.initials: A
authors.lastname: Frigessi
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Overgaard
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D008408:Mastectomy; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D015203:Reproducibility of Results; D012307:Risk Factors; D059467:Transcriptome; D016896:Treatment Outcome; D047368:Tumor Burden