title: A meta-analysis of gene expression-based biomarkers predicting outcome after tamoxifen treatment in breast cancer.
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.
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Mihály
authors.forename: Máté
authors.initials: M
authors.lastname: Kormos
authors.forename: András
authors.initials: A
authors.lastname: Lánczky
authors.forename: Magdolna
authors.initials: M
authors.lastname: Dank
authors.forename: Jan
authors.initials: J
authors.lastname: Budczies
authors.forename: Marcell A
authors.initials: MA
authors.lastname: Szász
authors.forename: Balázs
authors.initials: B
authors.lastname: Győrffy
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics; D011379:Prognosis; D011725:Pyridines / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage*; D016896:Treatment Outcome; D016875:tau Proteins / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D027283:Large Neutral Amino Acid-Transporter 1; C054369:MAPT protein, human; D011725:Pyridines; D016875:tau Proteins; D013629:Tamoxifen; C065523:1-(alpha-pyridine)-2-propanol