Comparison of gene expression profiles predicting progression in breast cancer patients treated with tamoxifen

Kok, Marleen; Linn, Sabine C.; Laar, Ryan K. van; Jansen, Maurice P.H.M.; Berg, Teun M. van den; Delahaye, Leonie; Glas, Annuska M.; Peterse, Johannes L.; Hauptmann, Michael; Foekens, John A.; Klijn, Jan G.M.; Wessels, Lodewyk; Veer, Laura J. van’t; Berns, Els M.J.J.

doi:10.1007/s10549-008-9939-y

Cited by 60 publications

(46 citation statements)

References 24 publications

(39 reference statements)

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“…Total tumor RNA was isolated as described previously (27). mRNA quality was assessed by quantitative real-time PCR (qRT-PCR) and bioanalyzer.…”

Section: Rna Isolation and Mrna Expression Analysismentioning

confidence: 99%

“…mRNA quality was assessed by quantitative real-time PCR (qRT-PCR) and bioanalyzer. Amplification, labeling, and hybridization of samples to 44k mRNA oligonucleotide-arrays (Agilent Technologies) were performed as described (27). Samples were hybridized against a breast cancer reference pool consisting of RNA from 105 primary breast tumors.…”

Section: Rna Isolation and Mrna Expression Analysismentioning

confidence: 99%

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Hallmarks of Aromatase Inhibitor Drug Resistance Revealed by Epigenetic Profiling in Breast Cancer

et al. 2013

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Aromatase inhibitors are the major first-line treatment of estrogen receptor-positive breast cancer, but resistance to treatment is common. To date, no biomarkers have been validated clinically to guide subsequent therapy in these patients. In this study, we mapped the genome-wide chromatin-binding profiles of estrogen receptor a (ERa), along with the epigenetic modifications H3K4me3 and H3K27me3, that are responsible for determining gene transcription (n ¼ 12). Differential binding patterns of ERa, H3K4me3, and H3K27me3 were enriched between patients with good or poor outcomes after aromatase inhibition. ERa and H3K27me3 patterns were validated in an additional independent set of breast cancer cases (n ¼ 10). We coupled these patterns to array-based proximal gene expression and progression-free survival data derived from a further independent cohort of 72 aromatase inhibitor-treated patients. Through this approach, we determined that the ERa and H3K27me3 profiles predicted the treatment outcomes for first-line aromatase inhibitors. In contrast, the H3K4me3 pattern identified was not similarly informative. The classification potential of these genes was only partially preserved in a cohort of 101 patients who received first-line tamoxifen treatment, suggesting some treatment selectivity in patient classification. Cancer Res; 73(22); 6632-41. Ó2013 AACR.

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“…Total tumor RNA was isolated as described previously (27). mRNA quality was assessed by quantitative real-time PCR (qRT-PCR) and bioanalyzer.…”

Section: Rna Isolation and Mrna Expression Analysismentioning

confidence: 99%

Section: Rna Isolation and Mrna Expression Analysismentioning

confidence: 99%

Hallmarks of Aromatase Inhibitor Drug Resistance Revealed by Epigenetic Profiling in Breast Cancer

et al. 2013

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“…Patients did not receive any systemic adjuvant treatment following surgery and/or radiotherapy, and tamoxifen was initiated as a first-line treatment of recurrent disease. For the purposes of this and previous studies (12,13), recurrences within 6 months of initiation of tamoxifen were classified as having a poor outcome (Amsterdam dataset n ¼ 21, Rotterdam dataset n ¼ 18), whereas those that showed no recurrence within the same time frame were classified as having a good outcome (Amsterdam dataset n ¼ 48, Rotterdam dataset n ¼ 22).…”

Section: Gene Expression Profilingmentioning

confidence: 99%

miR-187 Is an Independent Prognostic Factor in Breast Cancer and Confers Increased Invasive PotentialIn Vitro

Mulrane

Madden

Brennan

et al. 2012

Clinical Cancer Research

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Purpose: Here, we describe an integrated bioinformatics, functional analysis, and translational pathology approach to identify novel miRNAs involved in breast cancer progression.Experimental Design: Coinertia analysis (CIA) was used to combine a database of predicted miRNA target sites and gene expression data. Using two independent breast cancer cohorts, CIA was combined with correspondence analysis and between group analysis to produce a ranked list of miRNAs associated with disease progression. Ectopic expression studies were carried out in MCF7 cells and miRNA expression evaluated in two additional cohorts of patients with breast cancer by in situ hybridization on tissue microarrays.Results: CIA identified miR-187 as a key miRNA associated with poor outcome in breast cancer. Ectopic expression of miR-187 in breast cancer cells resulted in a more aggressive phenotype. In a test cohort (n ¼ 117), high expression of miR-187 was associated with a trend toward reduced breast cancer-specific survival (BCSS; P ¼ 0.058), and a significant association with reduced BCSS in lymph node-positive patients (P ¼ 0.036). In a validation cohort (n ¼ 470), high miR-187 was significantly associated with reduced BCSS in the entire cohort (P ¼ 0.021) and in lymph node-positive patients (P ¼ 0.012). Multivariate Cox regression analysis revealed that miR-187 is an independent prognostic factor in both cohorts [cohort 1: HR, 7.37; 95% confidence interval (CI), 2.05-26.51; P ¼ 0.002; cohort 2: HR, 2.80; 95% CI, 1.52-5.16; P ¼ 0.001] and in lymph node-positive patients in both cohorts (cohort 1: HR, 13.74; 95% CI, 2.62-72.03; P ¼ 0.002; cohort 2: HR, 2.77; 95% CI, 1.32-5.81; P ¼ 0.007).Conclusions: miR-187 expression in breast cancer leads to a more aggressive, invasive phenotype and acts as an independent predictor of outcome. Clin Cancer Res; 18(24); 6702-13. Ó2012 AACR.

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“…The gene expression signature predicts that 70-80% of these patients are unlikely to develop metastasis, so these patients are currently overtreated. Several other gene expression profiles predict recurrence and overall survival and/or tamoxifen resistance (Ma et al 2004, Paik et al 2004, Jansen et al 2005, Wang et al 2005, Frasor et al 2006, Oh et al 2006, Gräf et al 2007, Chanrion et al 2008, Kok et al 2009, Lippman et al 2008, Zhang et al 2009). …”

Section: Era Target Genes and Breast Cancermentioning

confidence: 99%

Genomic actions of estrogen receptor α: what are the targets and how are they regulated?

Welboren

Sweep²,

Span³

et al. 2009

Endocrine-Related Cancer

142

113

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The estrogen receptor a (ERa) is a ligand-dependent transcription factor that regulates a large number of genes in many different target tissues and is important in the development and progression of breast cancer. ERa-mediated transcription is a complex process regulated at many different levels. The interplay between ligand, receptor, DNA sequence, cofactors, chromatin context, and post-translational modifications culminates in transcriptional regulation by ERa. Recent technological advances have allowed the identification of ERa target genes on a genomewide scale. In this review, we provide an overview of the progress made in our understanding of the different levels of regulation mediated by ERa. We discuss the recent advances in the identification of the ERa-binding sites and target gene network and their clinical applications.

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Comparison of gene expression profiles predicting progression in breast cancer patients treated with tamoxifen

Cited by 60 publications

References 24 publications

Hallmarks of Aromatase Inhibitor Drug Resistance Revealed by Epigenetic Profiling in Breast Cancer

Hallmarks of Aromatase Inhibitor Drug Resistance Revealed by Epigenetic Profiling in Breast Cancer

miR-187 Is an Independent Prognostic Factor in Breast Cancer and Confers Increased Invasive PotentialIn Vitro

Genomic actions of estrogen receptor α: what are the targets and how are they regulated?

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