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Rigshospitalet - a part of Copenhagen University Hospital
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Predicting efficacy of epirubicin by a multigene assay in advanced breast cancer within a Danish Breast Cancer Cooperative Group (DBCG) cohort: a retrospective-prospective blinded study

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  • Anna Sofie Kappel Buhl
  • Troels Dreier Christensen
  • Ib Jarle Christensen
  • Knud Mejer Nelausen
  • Eva Balslev
  • Ann Søegaard Knoop
  • Eva Harder Brix
  • Else Svensson
  • Vesna Glavicic
  • Adam Luczak
  • Sven Tyge Langkjer
  • Søren Linnet
  • Erik Hugger Jakobsen
  • Jurij Bogovic
  • Bent Ejlertsen
  • Annie Rasmussen
  • Anker Hansen
  • Steen Knudsen
  • Dorte Nielsen
  • Peter Buhl Jensen
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PURPOSE: Anthracyclines remain a cornerstone in the treatment of primary and advanced breast cancer (BC). This study has evaluated the predictive value of a multigene mRNA-based drug response predictor (DRP) in the treatment of advanced BC with epirubicin. The DRP is a mathematical method combining in vitro sensitivity and gene expression with clinical genetic information from > 3000 clinical tumor samples.

METHODS: From a DBCG cohort, 140 consecutive patients were treated with epirubicin between May 1997 and November 2016. After patient informed consent, mRNA was isolated from archival formalin-fixed paraffin-embedded primary breast tumor tissue and analyzed using Affymetrix arrays. Using time to progression (TTP) as primary endpoint, the efficacy of epirubicin was analyzed according to DRP combined with clinicopathological data collected retrospectively from patients' medical records. Statistical analysis was done using Cox proportional hazards model stratified by treatment line.

RESULTS: Median TTP was 9.3 months. The DRP was significantly associated to TTP (P = 0.03). The hazard ratio for DRP scores differing by 50 percentage points was 0.55 (95% CI -0.93, one-sided). A 75% DRP was associated with a median TTP of 13 months compared to 7 months following a 25% DRP. Multivariate analysis showed that DRP was independent of age and number of metastases.

CONCLUSION: The current study prospectively validates the predictive capability of DRP regarding epirubicin previously shown retrospectively allowing the patients predicted to be poor responders to choose more effective alternatives. Randomized prospective studies are needed to demonstrate if such an approach will lead to increased overall survival.

Original languageEnglish
JournalBreast Cancer Research and Treatment
Volume172
Issue number2
Pages (from-to)391-400
ISSN0167-6806
DOIs
Publication statusPublished - 2018

ID: 55423734