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Lei et al. J Cancer Metastasis Treat 2019;5:38 Journal of Cancer
DOI: 10.20517/2394-4722.2019.12 Metastasis and Treatment

Review Open Access

ESR1 alterations and metastasis in estrogen
receptor positive breast cancer

Jonathan T. Lei , Xuxu Gou , Sinem Seker , Matthew J. Ellis 1,2,3
1,2
1,2
2
1 Interdepartmental Graduate Program in Translational Biology & Molecular Medicine, Baylor College of Medicine, Houston, TX
77030, USA.
2 Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
3 Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Correspondence to: Dr. Jonathan T. Lei, Interdepartmental Graduate Program in Translational Biology & Molecular Medicine,
Baylor College of Medicine, Houston, TX 77030, USA. E-mail: jlei@bcm.edu

How to cite this article: Lei JT, Gou X, Seker S, Ellis MJ. ESR1 alterations and metastasis in estrogen receptor positive breast
cancer. J Cancer Metastasis Treat 2019;5:38. http://dx.doi.org/10.20517/2394-4722.2019.12

Received: 1 Feb 2019 First Decision: 25 Feb 2019 Revised: 26 Mar 2019 Accepted: 4 Apr 2019 Published: 4 May 2019
Science Editor: William Schiemann Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Endocrine therapy is essential for the treatment of patients with estrogen receptor positive (ER+) breast cancer,
however, resistance and the development of metastatic disease is common. Understanding how ER+ breast cancer
metastasizes is critical since the major cause of death in breast cancer is metastasis to distant organs. Results
from many studies suggest dysregulation of the estrogen receptor alpha gene (ESR1) contributes to therapeutic
resistance and metastatic biology. This review covers both pre-clinical and clinical evidence on the spectrum of ESR1
alterations including amplification, point mutations, and genomic rearrangement events driving treatment resistance
and metastatic potential of ER+ breast cancer. Importantly, we describe how these ESR1 alterations may provide
therapeutic opportunities to improve outcomes in patients with lethal, metastatic breast cancer.

Keywords: Endocrine therapy resistance, ESR1 fusions, ESR1 mutations, breast cancer, metastasis

INTRODUCTION
Breast cancer is one of the leading cancer-related causes of death worldwide with more than one million new
cases and more than 450,000 deaths per year according to the World Health Organization. About 70% of
[1]
diagnosed cases express estrogen receptor alpha (ER) , where ER signaling is the defining and driving event
contributing to tumor growth and disease progression in these ER+ breast tumors.

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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and indicate if changes were made.

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