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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: a retrospective-prospective blinded study

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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: 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
Source: Breast Cancer Res Treat
Buhl, A S K, Christensen, T D, Christensen, I J, Nelausen, K M, Balslev, E, Knoop, A S, Brix, E H, Svensson, E, Glavicic, V, Luczak, A, Langkjer, S T, Linnet, S, Jakobsen, E H, Bogovic, J, Ejlertsen, B, Rasmussen, A, Hansen, A, Knudsen, S, Nielsen, D & Jensen, P B 2018, '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', Breast Cancer Research and Treatment, vol. 172, no. 2, pp. 391–400. https://doi.org/10.1007/s10549-018-4918-4
Buhl, A S K, Christensen, T D, Christensen, I J, Nelausen, K M, Balslev, E, Knoop, A S, Brix, E H, Svensson, E, Glavicic, V, Luczak, A, Langkjer, S T, Linnet, S, Jakobsen, E H, Bogovic, J, Ejlertsen, B, Rasmussen, A, Hansen, A, Knudsen, S, Nielsen, D & Jensen, P B 2018, ' 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 ', Breast Cancer Research and Treatment, vol. 172, no. 2, pp. 391–400 . https://doi.org/10.1007/s10549-018-4918-4
Buhl, A S K, Christensen, T D, Christensen, I J, Nelausen, K M, Balslev, E, Knoop, A S, Brix, E H, Svensson, E, Glavicic, V, Luczak, A, Langkjer, S T, Linnet, S, Jakobsen, E H, Bogovic, J, Ejlertsen, B, Rasmussen, A, Hansen, A, Knudsen, S, Nielsen, D & Jensen, P B 2018, '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', Breast Cancer Research and Treatment, vol. 172, no. 2, pp. 391-400. https://doi.org/10.1007/s10549-018-4918-4
Buhl, A S K, Christensen, T D, Christensen, I J, Nelausen, K M, Balslev, E, Knoop, A S, Brix, E H, Svensson, E, Glavicic, V, Luczak, A, Langkjer, S T, Linnet, S, Jakobsen, E H, Bogovic, J, Ejlertsen, B, Rasmussen, A, Hansen, A, Knudsen, S, Nielsen, D & Jensen, P B 2018, ' 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 ', Breast Cancer Research and Treatment, vol. 172, no. 2, pp. 391-400 . https://doi.org/10.1007/s10549-018-4918-4
Publisher Information: Springer Science and Business Media LLC, 2018.
Publication Year: 2018
Subject Terms: RNA, Messenger/genetics, Adult, Epirubicin/administration & dosage, Breast Neoplasms, Biomarkers, Pharmacological, Disease-Free Survival, Neoplastic/drug effects, 03 medical and health sciences, 0302 clinical medicine, Breast Neoplasms/drug therapy, Neoplasm Proteins/genetics, Humans, Prospective Studies, RNA, Messenger, Precision Medicine, Aged, Epirubicin, Proportional Hazards Models, Retrospective Studies, Pharmacological, Precision medicine, Middle Aged, Clinical Trial, Neoplasm Proteins, 3. Good health, Gene Expression Regulation, Neoplastic, Predictive biomarker, Gene Expression Regulation, Gene Expression Regulation, Neoplastic/drug effects, Disease Progression, RNA, Messenger/genetics, Advanced breast cancer, Female, Biomarkers
Description: 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.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.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.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.
Document Type: Article
Other literature type
File Description: application/pdf
Language: English
ISSN: 1573-7217
0167-6806
DOI: 10.1007/s10549-018-4918-4
Access URL: https://link.springer.com/content/pdf/10.1007/s10549-018-4918-4.pdf
https://pubmed.ncbi.nlm.nih.gov/30099635
https://vbn.aau.dk/da/publications/predicting-efficacy-of-epirubicin-by-a-multigene-assay-in-advance
https://link.springer.com/content/pdf/10.1007/s10549-018-4918-4.pdf
https://link.springer.com/article/10.1007/s10549-018-4918-4
https://europepmc.org/article/MED/30099635
https://link.springer.com/article/10.1007/s10549-018-4918-4/fulltext.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208899
https://pure.au.dk/ws/files/167672692/Buhl2018_Article_PredictingEfficacyOfEpirubicin.pdf
https://curis.ku.dk/ws/files/222252352/Buhl2018_Article_PredictingEfficacyOfEpirubicin.pdf
https://findresearcher.sdu.dk:8443/ws/files/146451348/Buhl2018_Article_PredictingEfficacyOfEpirubicin.pdf
Rights: CC BY
Accession Number: edsair.doi.dedup.....5f4d0f127f0dafb654c610d7a725c80a
Database: OpenAIRE
Description
Abstract: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.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.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.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.
ISSN:15737217
01676806
DOI:10.1007/s10549-018-4918-4