Gene expression signatures that predict outcome of tamoxifen-treated estrogen receptor-positive, high-risk, primary breast cancer patients: a DBCG study.

<h4>Background</h4>Tamoxifen significantly improves outcome for estrogen receptor-positive (ER+) breast cancer, but the 15-year recurrence rate remains 30%. The aim of this study was to identify gene profiles that accurately predicted the outcome of ER+ breast cancer patients who receive...

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Autores principales:	Maria B Lyng, Anne-Vibeke Lænkholm, Qihua Tan, Werner Vach, Karina H Gravgaard, Ann Knoop, Henrik J Ditzel
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4df9fac58d304b538316d6aa19a77ca8
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spelling	oai:doaj.org-article:4df9fac58d304b538316d6aa19a77ca82021-11-18T08:01:12ZGene expression signatures that predict outcome of tamoxifen-treated estrogen receptor-positive, high-risk, primary breast cancer patients: a DBCG study.1932-620310.1371/journal.pone.0054078https://doaj.org/article/4df9fac58d304b538316d6aa19a77ca82013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23342080/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Tamoxifen significantly improves outcome for estrogen receptor-positive (ER+) breast cancer, but the 15-year recurrence rate remains 30%. The aim of this study was to identify gene profiles that accurately predicted the outcome of ER+ breast cancer patients who received adjuvant Tamoxifen mono-therapy.<h4>Methodology/principal findings</h4>Post-menopausal breast cancer patients diagnosed no later than 2002, being ER+ as defined by >1% IHC staining and having a frozen tumor sample with >50% tumor content were included. Tumor samples from 108 patients treated with adjuvant Tamoxifen were analyzed for the expression of 59 genes using quantitative-PCR. End-point was clinically verified recurrence to distant organs or ipsilateral breast. Gene profiles were identified using a model building procedure based on conditional logistic regression and leave-one-out cross-validation, followed by a non-parametric bootstrap (1000x re-sampling). The optimal profiles were further examined in 5 previously-reported datasets containing similar patient populations that were either treated with Tamoxifen or left untreated (n = 623). Three gene signatures were identified, the strongest being a 2-gene combination of BCL2-CDKN1A, exhibiting an accuracy of 75% for prediction of outcome. Independent examination using 4 previously-reported microarray datasets of Tamoxifen-treated patient samples (n = 503) confirmed the potential of BCL2-CDKN1A. The predictive value was further determined by comparing the ability of the genes to predict recurrence in an additional, previously-published, cohort consisting of Tamoxifen-treated (n = 58, p = 0.015) and untreated patients (n = 62, p = 0.25).<h4>Conclusions/significance</h4>A novel gene expression signature predictive of outcome of Tamoxifen-treated patients was identified. The validation suggests that BCL2-CDKN1A exhibit promising predictive potential.Maria B LyngAnne-Vibeke LænkholmQihua TanWerner VachKarina H GravgaardAnn KnoopHenrik J DitzelPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e54078 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maria B Lyng Anne-Vibeke Lænkholm Qihua Tan Werner Vach Karina H Gravgaard Ann Knoop Henrik J Ditzel Gene expression signatures that predict outcome of tamoxifen-treated estrogen receptor-positive, high-risk, primary breast cancer patients: a DBCG study.
description	<h4>Background</h4>Tamoxifen significantly improves outcome for estrogen receptor-positive (ER+) breast cancer, but the 15-year recurrence rate remains 30%. The aim of this study was to identify gene profiles that accurately predicted the outcome of ER+ breast cancer patients who received adjuvant Tamoxifen mono-therapy.<h4>Methodology/principal findings</h4>Post-menopausal breast cancer patients diagnosed no later than 2002, being ER+ as defined by >1% IHC staining and having a frozen tumor sample with >50% tumor content were included. Tumor samples from 108 patients treated with adjuvant Tamoxifen were analyzed for the expression of 59 genes using quantitative-PCR. End-point was clinically verified recurrence to distant organs or ipsilateral breast. Gene profiles were identified using a model building procedure based on conditional logistic regression and leave-one-out cross-validation, followed by a non-parametric bootstrap (1000x re-sampling). The optimal profiles were further examined in 5 previously-reported datasets containing similar patient populations that were either treated with Tamoxifen or left untreated (n = 623). Three gene signatures were identified, the strongest being a 2-gene combination of BCL2-CDKN1A, exhibiting an accuracy of 75% for prediction of outcome. Independent examination using 4 previously-reported microarray datasets of Tamoxifen-treated patient samples (n = 503) confirmed the potential of BCL2-CDKN1A. The predictive value was further determined by comparing the ability of the genes to predict recurrence in an additional, previously-published, cohort consisting of Tamoxifen-treated (n = 58, p = 0.015) and untreated patients (n = 62, p = 0.25).<h4>Conclusions/significance</h4>A novel gene expression signature predictive of outcome of Tamoxifen-treated patients was identified. The validation suggests that BCL2-CDKN1A exhibit promising predictive potential.
format	article
author	Maria B Lyng Anne-Vibeke Lænkholm Qihua Tan Werner Vach Karina H Gravgaard Ann Knoop Henrik J Ditzel
author_facet	Maria B Lyng Anne-Vibeke Lænkholm Qihua Tan Werner Vach Karina H Gravgaard Ann Knoop Henrik J Ditzel
author_sort	Maria B Lyng
title	Gene expression signatures that predict outcome of tamoxifen-treated estrogen receptor-positive, high-risk, primary breast cancer patients: a DBCG study.
title_short	Gene expression signatures that predict outcome of tamoxifen-treated estrogen receptor-positive, high-risk, primary breast cancer patients: a DBCG study.
title_full	Gene expression signatures that predict outcome of tamoxifen-treated estrogen receptor-positive, high-risk, primary breast cancer patients: a DBCG study.
title_fullStr	Gene expression signatures that predict outcome of tamoxifen-treated estrogen receptor-positive, high-risk, primary breast cancer patients: a DBCG study.
title_full_unstemmed	Gene expression signatures that predict outcome of tamoxifen-treated estrogen receptor-positive, high-risk, primary breast cancer patients: a DBCG study.
title_sort	gene expression signatures that predict outcome of tamoxifen-treated estrogen receptor-positive, high-risk, primary breast cancer patients: a dbcg study.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/4df9fac58d304b538316d6aa19a77ca8
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Gene expression signatures that predict outcome of tamoxifen-treated estrogen receptor-positive, high-risk, primary breast cancer patients: a DBCG study.

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