A meta-analysis of gene expression-based biomarkers predicting outcome after tamoxifen treatment in breast cancer.

TitleA meta-analysis of gene expression-based biomarkers predicting outcome after tamoxifen treatment in breast cancer.
Publication TypeJournal Article
Year of Publication2013
AuthorsMihály Z, Kormos M, Lánczky A, Dank M, Budczies J, Szász MA, Győrffy B
JournalBreast Cancer Res Treat
Volume140
Issue2
Pagination219-32
Date Published2013 Jul
ISSN1573-7217
Abstract

To date, three molecular markers (ER, PR, and CYP2D6) have been used in clinical setting to predict the benefit of the anti-estrogen tamoxifen therapy. Our aim was to validate new biomarker candidates predicting response to tamoxifen treatment in breast cancer by evaluating these in a meta-analysis of available transcriptomic datasets with known treatment and follow-up. Biomarker candidates were identified in Pubmed and in the 2007-2012 ASCO and 2011-2012 SABCS abstracts. Breast cancer microarray datasets of endocrine therapy-treated patients were downloaded from GEO and EGA and RNAseq datasets from TCGA. Of the biomarker candidates, only those identified or already validated in a clinical cohort were included. Relapse-free survival (RFS) up to 5 years was used as endpoint in a ROC analysis in the GEO and RNAseq datasets. In the EGA dataset, Kaplan-Meier analysis was performed for overall survival. Statistical significance was set at p < 0.005. The transcriptomic datasets included 665 GEO-based and 1,208 EGA-based patient samples. All together 68 biomarker candidates were identified. Of these, the best performing genes were PGR (AUC = 0.64, p = 2.3E-07), MAPT (AUC = 0.62, p = 7.8E-05), and SLC7A5 (AUC = 0.62, p = 9.2E-05). Further genes significantly correlated to RFS include FOS, TP53, BTG2, HOXB7, DRG1, CXCL10, and TPM4. In the RNAseq dataset, only ERBB2, EDF1, and MAPK1 reached statistical significance. We evaluated tamoxifen-resistance genes in three independent platforms and identified PGR, MAPT, and SLC7A5 as the most promising prognostic biomarkers in tamoxifen treated patients.

DOI10.1007/s10549-013-2622-y
Alternate JournalBreast Cancer Res. Treat.
PubMed ID23836010