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Open Access 01-11-2018 | Clinical trial

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

Authors: 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

Published in: Breast Cancer Research and Treatment | Issue 2/2018

Abstract

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.

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Title: 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
Authors: 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
Publication date: 01-11-2018
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 2/2018
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-4918-4

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