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The Evolving Role of the Estrogen Receptor Mutations in Endocrine Therapy-Resistant Breast Cancer

  • Breast Cancer (B Overmoyer, Section Editor)
  • Published:
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Abstract

Recurrent ligand-binding domain ESR1 mutations have recently been detected in a substantial number of patients with metastatic ER+ breast cancer and evolve under the selective pressure of endocrine treatments. In this review, we evaluate the current understanding of the biological and clinical significance of these mutations. The preclinical studies revealed that these mutations lead to constitutive ligand-independent activity, indicating resistance to aromatase inhibitors and decreased sensitivity to tamoxifen and fulvestrant. Retrospective analyses of ESR1 mutations in baseline plasma circulating tumor DNA from completed clinical trials suggest that these mutations are prognostic and predictive of resistance to aromatase inhibitors in metastatic disease. Currently, we are lacking prospective studies to confirm these results and to determine the optimal treatment combinations for patients with the ESR1 mutations. In addition, the clinical development of novel agents to overcome resistance engendered by these mutations is also needed.

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Acknowledgements

This paper was supported by the NCI Grant K08 CA191058-02 (R.J.), the Breast Cancer Alliance Exceptional Award Grant (R.J.), the Breast Cancer Research Foundation (R.S.), NIH Breast Cancer Specialized Programs of Research Excellence Grants P50CA058183 and P50CA186784 (R.S.), NIH Cancer Center Grant P30CA125123, Susan G. Komen for the Cure Foundation Promise Grants PG12221410 (R.S.), and the Conquer Cancer Foundation (C.D.A., Breast Cancer Research Fellowship).

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Authors and Affiliations

  1. Breast Oncology Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA

    Rinath Jeselsohn & Myles Brown

  2. Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA

    Rinath Jeselsohn & Myles Brown

  3. Smith Breast Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA

    Carmine De Angelis & Rachel Schiff

  4. Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA

    Carmine De Angelis & Rachel Schiff

  5. Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA

    Carmine De Angelis & Rachel Schiff

  6. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA

    Carmine De Angelis & Rachel Schiff

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  1. Rinath Jeselsohn
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  2. Carmine De Angelis
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  4. Rachel Schiff
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Correspondence to Rinath Jeselsohn.

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Rinath Jeselsohn declares no conflict of interest.

Carmine De Angelis declares that he has no conflict of interest.

Myles Brown declares that he has no conflict of interest.

Rachel Schiff has received research support through grants from Gilead and AstraZeneca.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Breast Cancer

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Jeselsohn, R., De Angelis, C., Brown, M. et al. The Evolving Role of the Estrogen Receptor Mutations in Endocrine Therapy-Resistant Breast Cancer. Curr Oncol Rep 19, 35 (2017). https://doi.org/10.1007/s11912-017-0591-8

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  • DOI: https://doi.org/10.1007/s11912-017-0591-8

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