Estrogen Receptor Alpha Gene Amplification in Breast Cancer: 25 Years of Debate

Overview

Journal World J Clin Oncol

Publisher Baishideng Publishing Group

Specialty Oncology

Date 2016 Apr 16

PMID 27081639

Citations 12

Authors

Frederik Holst

Affiliations

Soon will be listed here.

Abstract

Twenty-five years ago, Nembrot and colleagues reported amplification of the estrogen receptor alpha gene (ESR1) in breast cancer, initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration, which affects one of the most important genes in breast cancer. Since then, a multitude of studies on this topic has been published, covering a wide range of divergent results and arguments. The reported prevalence of this alteration in breast cancer ranges from 0% to 75%, suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues. To date, two major issues related to ESR1 amplification remain to be conclusively addressed: (1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1, and (2) the clinical relevance of ESR1 amplification: Such relevance is strongly disputed, with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies, or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1. This review provides a comprehensive summary of the various views on ESR1 amplification, and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research.

Citing Articles

Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer.

Singer C, Holst F, Steurer S, Burandt E, Lax S, Jakesz R Clin Cancer Res. 2022; 28(18):4112-4120.

PMID: 35920686 PMC: 9475247. DOI: 10.1158/1078-0432.CCR-21-4328.

Regulation of Bcl-2 Family Proteins in Estrogen Receptor-Positive Breast Cancer and Their Implications in Endocrine Therapy.

Kawiak A, Kostecka A Cancers (Basel). 2022; 14(2).

PMID: 35053443 PMC: 8773933. DOI: 10.3390/cancers14020279.

Comprehensive molecular profiling of Taiwanese breast cancers revealed potential therapeutic targets: prevalence of actionable mutations among 380 targeted sequencing analyses.

Huang C, Tsai Y, Liu C, Chao T, Lien P, Lin Y BMC Cancer. 2021; 21(1):199.

PMID: 33632156 PMC: 7908797. DOI: 10.1186/s12885-021-07931-4.

Mutations Are Not a Common Mechanism of Endocrine Resistance in Patients With Estrogen Receptor-Positive Breast Cancer Treated With Neoadjuvant Aromatase Inhibitor Therapy.

Reinert T, Ramalho S, de Vasconcelos V, Silva L, da Silva A, de Andrade C Front Oncol. 2020; 10:342.

PMID: 32309212 PMC: 7145981. DOI: 10.3389/fonc.2020.00342.

Association of Mutations and Visceral Metastasis in Patients with Estrogen Receptor-Positive Advanced Breast Cancer from Brazil.

Reinert T, Coelho G, Mandelli J, Zimermann E, Zaffaroni F, Bines J J Oncol. 2019; 2019:1947215.

PMID: 31511774 PMC: 6710809. DOI: 10.1155/2019/1947215.

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