Hormones and Cancer

, Volume 9, Issue 4, pp 215–228 | Cite as

The Impact of ESR1 Mutations on the Treatment of Metastatic Breast Cancer

  • Sasha M. Pejerrey
  • Derek Dustin
  • Jin-Ah Kim
  • Guowei Gu
  • Yassine Rechoum
  • Suzanne A. W. FuquaEmail author


After nearly 20 years of research, it is now established that mutations within the estrogen receptor (ER) gene, ESR1, frequently occur in metastatic breast cancer and influence response to hormone therapy. Though early studies presented differing results, sensitive sequencing techniques now show that ESR1 mutations occur at a frequency between 20 and 40% depending on the assay method. Recent studies have focused on several “hot spot mutations,” a cluster of mutations found in the hormone-binding domain of the ESR1 gene. Throughout the course of treatment, tumor evolution can occur, and ESR1 mutations emerge and become enriched in the metastatic setting. Sensitive techniques to continually monitor mutant burden in vivo are needed to effectively treat patients with mutant ESR1. The full impact of these mutations on tumor response to different therapies remains to be determined. However, recent studies indicate that mutant-bearing tumors may be less responsive to specific hormonal therapies, and suggest that aromatase inhibitor (AI) therapy may select for the emergence of ESR1 mutations. Additionally, different mutations may respond discretely to targeted therapies. The need for more preclinical mechanistic studies on ESR1 mutations and the development of better agents to target these mutations are urgently needed. In the future, sequential monitoring of ESR1 mutational status will likely direct personalized therapeutic regimens appropriate to each tumor’s unique mutational landscape.


Funding Information

The study received funding from the National Institutes of Health NCI RO1 CA207270, Breast Cancer Research Foundation 16-056, National Institutes of Health NCI R01CA072038, and Cancer Prevention Research Institute of Texas RP150440.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Lester and Sue Smith Breast CenterBaylor College of MedicineHoustonUSA

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