ArticlePloS one2013
Prognostic significance of ESR1 gene amplification, mRNA/protein expression and functional profiles in high-risk early breast cancer: a translational study of the Hellenic Cooperative Oncology Group (HeCOG).
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Evaluation of the prognostic value of CD3, CD8, and FOXP3 mRNA expression in early-stage breast cancer patients treated with anthracycline-based adjuvant chemotherapy.Cancer medicine · 2018Trial
- Association of osteopontin with specific prognostic factors and survival in adjuvant breast cancer trials of the Hellenic Cooperative Oncology Group.Journal of translational medicine · 2017Trial
- Review
- Analysis of the prognostic relevance of sex-steroid hormonal receptor mRNA expression in muscle-invasive urothelial carcinoma of the urinary bladder.Virchows Archiv : an international journal of pathology · 2019Article
- Evaluation of the Prognostic Value of RANK, OPG, and RANKL mRNA Expression in Early Breast Cancer Patients Treated with Anthracycline-Based Adjuvant Chemotherapy.Translational oncology · 2017Article
- Estrogen receptor alpha gene amplification in breast cancer: 25 years of debate.World journal of clinical oncology · 2016Review
- Article
- Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Evaluation of the prognostic significance of HER family mRNA expression in high-risk early breast cancer: a Hellenic Cooperative Oncology Group (HeCOG) validation study.Journal of translational medicine · 2015Article
- Pharmacodynamic imaging guides dosing of a selective estrogen receptor degrader.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- ESR1 amplification in breast cancer by optimized RNase FISH: frequent but low-level and heterogeneous.PloS one · 2013Article
Corrections and comments
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Authors and funding
22 authors at 11 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiscrepant data have been published on the incidence and prognostic significance of ESR1 gene amplification in early breast cancer. PATIENTS AND
methodsFormalin-fixed paraffin-embedded tumor blocks were collected from women with early breast cancer participating in two HeCOG adjuvant trials. Messenger RNA was studied by quantitative PCR, ER protein expression was centrally assessed using immunohistochemistry (IHC) and ESR1 gene copy number by dual fluorescent in situ hybridization probes.
resultsIn a total of 1010 women with resected node-positive early breast adenocarcinoma, the tumoral ESR1/CEP6 gene ratio was suggestive of deletion in 159 (15.7%), gene gain in 551 (54.6%) and amplification in 42 cases (4.2%), with only 30 tumors (3%) harboring five or more ESR1 copies. Gene copy number ratio showed a significant, though weak correlation to mRNA and protein expression (Spearman's Rho <0.23, p = 0.01). ESR1 clusters were observed in 9.5% (57 gain, 38 amplification) of cases. In contrast to mRNA and protein expression, which were favorable prognosticators, gene copy number changes did not obtain prognostic significance. When ESR1/CEP6 gene ratio was combined with function (as defined by ER protein and mRNA expression) in a molecular classifier, the Gene Functional profile, it was functional status that impacted on prognosis. In univariate analysis, patients with functional tumors (positive ER protein expression and gene ratio normal or gain/amplification) fared better than those with non-functional tumors with ESR1 gain (HR for relapse or death 0.49-0.64, p = 0.003). Significant interactions were observed between gene gain/amplification and paclitaxel therapy (trend for DFS benefit from paclitaxel only in patients with ESR1 gain/amplification, p = 0.066) and Gene Functional profile with HER2 amplification (Gene Functional profile prognostic only in HER2-normal cases, p = 0.029).
conclusionsESR1 gene deletion and amplification do not constitute per se prognostic markers, instead they can be classified to distinct prognostic groups according to their protein-mediated functional status.
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