Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA103889 | ENA |
REPOSITORIES: ENA
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Project description:dataset of 60 patients with ER-positive primary breast cancer and treated with tamoxifen monotherapy for 5 years. Data were generated from LCMed cancer cells. Sample_keyword: breast cancer, tamoxifen, recurrence Keywords: other
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Project description:dataset of 60 patients with ER-positive primary breast cancer and treated with tamoxifen monotherapy for 5 years. Data were generated from whole tissue sections of breast cancers. Sample_keyword: breast cancer, tamoxifen, recurrence Keywords: other
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Project description:Adjuvant tamoxifen is a valid treatment option for women with estrogen receptor (ER)-positive breast cancer. However, up to 40% of patients experience distant or local recurrence or die. MicroRNAs have been suggested to be important prognosticators in breast cancer. This study aims to identify microRNAs with the potential to predict tamoxifen response. We performed a global microRNA screen in primary tumours of six matched pairs of postmenopausal, ER-positive breast cancer patients treated with tamoxifen, who were either recurrence free or had developed a recurrence. Patients were treated at the Robert Bosch Hospital, Stuttgart, Germany, between 1986 and 2005.
2014-07-01 | GSE46823 | GEO
Project description:Adjuvant tamoxifen is a valid treatment option for women with estrogen receptor (ER)-positive breast cancer. However, up to 40% of patients experience distant or local recurrence or die. MicroRNAs have been suggested to be important prognosticators in breast cancer. This study aims to identify microRNAs with the potential to predict tamoxifen response. We performed a global microRNA screen in primary tumours of six matched pairs of postmenopausal, ER-positive breast cancer patients treated with tamoxifen, who were either recurrence free or had developed a recurrence. Patients were treated at the Robert Bosch Hospital, Stuttgart, Germany, between 1986 and 2005. Total RNA from FFPE tissue from 12 postmenopausal patients with ER-positive breast cancer (6 patients with and 6 patients without recurrence) was extracted. Hybridisation of biotin-labelled RNA was performed on Affymetrix GeneChip miRNA_2.0 Arrays.
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Project description:Purpose: Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients treated with adjuvant Tamoxifen with regards to probability of recurrence. Experimental design: Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by 2 independent test sets (N=60 and N=40). All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half had developed distant recurrence (median time-to-recurrence: 3.5 years). MiRNA expression was examined by unsupervised hierarchical clustering and supervised analysis, including clinical parameters as co-variables.
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Project description:Endocrine resistance in breast cancer is a major clinical problem with poorly understood mechanisms. Mass spectrometry-based proteomics of a clinically-relevant tamoxifen-resistant cell line model identified increased levels of minichromosome maintenance proteins (MCM), including MCM3, as central in cell cycle and DNA replication protein-protein interaction networks associated with tamoxifen resistance. Lowering MCM3 protein expression in tamoxifen-resistant cells restored tamoxifen sensitivity and altered phosphorylation of several cell cycle regulators, such as p53(Ser315, 33), CHK1(Ser317) and cdc25b(Ser323), suggesting that MCM3 activation of important cell cycle-associated proteins overcomes tamoxifen’s anti-proliferative effects. High MCM3 expression in primary tumor tissue from two independent cohorts of ER+ breast cancer patients receiving adjuvant tamoxifen mono-therapy was an independent prognostic marker significantly associated with a shorter recurrence-free survival.
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