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Case report
peer-reviewed

Estradiol as a Targeted, Late-Line Therapy in Metastatic Breast Cancer with Estrogen Receptor Amplification



Abstract

Estradiol is a major regulator of growth for the subset of breast cancers that express the estrogen receptor (ER, ESR1). Strategies to block ER action, via reduction of estradiol or direct inhibition of ER, have shown major success in the prevention and treatment of breast cancer. However, most ER-positive (ER+) metastatic breast cancers (MBC) eventually become resistant to these interventions. Interestingly, high dose estrogen can induce apoptosis in breast cancer cell lines, and high-dose estrogen has been used for over 50 years as therapy for ER+ breast cancer. The mechanism for growth control of MBC by high dose estrogen is unclear. We present a patient with metastatic breast cancer whose tumor was found to have amplification of ESR1 by tumor genome sequencing. This patient was treated with high dose estradiol and subsequently experienced a sustained partial response, which was predicted by prior experiments with patient-derived xenograft animal models containing breast cancers with ER amplification.



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Case report
peer-reviewed

Estradiol as a Targeted, Late-Line Therapy in Metastatic Breast Cancer with Estrogen Receptor Amplification


Author Information

Karthik Kota Corresponding Author

Internal Medicine, UPMC Presbyterian

Adam Brufsky

Division of Hematology/Oncology, Magee Women's Hospital of UPMC

Steffi Oesterreich

Pharmacology and Chemical Biology, University Of Pittsburgh

Adrian Lee

Pharmacology and Chemical Biology, University Of Pittsburgh


Ethics Statement and Conflict of Interest Disclosures

Human subjects: Consent was obtained by all participants in this study. Conflicts of interest: The authors have declared that no conflicts of interest exist.


Case report
peer-reviewed

Estradiol as a Targeted, Late-Line Therapy in Metastatic Breast Cancer with Estrogen Receptor Amplification


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Case report
peer-reviewed

Estradiol as a Targeted, Late-Line Therapy in Metastatic Breast Cancer with Estrogen Receptor Amplification

  • Author Information
    Karthik Kota Corresponding Author

    Internal Medicine, UPMC Presbyterian

    Adam Brufsky

    Division of Hematology/Oncology, Magee Women's Hospital of UPMC

    Steffi Oesterreich

    Pharmacology and Chemical Biology, University Of Pittsburgh

    Adrian Lee

    Pharmacology and Chemical Biology, University Of Pittsburgh


    Ethics Statement and Conflict of Interest Disclosures

    Human subjects: Consent was obtained by all participants in this study. Conflicts of interest: The authors have declared that no conflicts of interest exist.

    Acknowledgements


    Article Information

    Published: July 06, 2017

    DOI

    10.7759/cureus.1434

    Cite this article as:

    Kota K, Brufsky A, Oesterreich S, et al. (July 06, 2017) Estradiol as a Targeted, Late-Line Therapy in Metastatic Breast Cancer with Estrogen Receptor Amplification. Cureus 9(7): e1434. doi:10.7759/cureus.1434

    Publication history

    Received by Cureus: May 24, 2017
    Peer review began: June 07, 2017
    Peer review concluded: July 05, 2017
    Published: July 06, 2017

    Copyright

    © Copyright 2017
    Kota et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 3.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    License

    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Estradiol is a major regulator of growth for the subset of breast cancers that express the estrogen receptor (ER, ESR1). Strategies to block ER action, via reduction of estradiol or direct inhibition of ER, have shown major success in the prevention and treatment of breast cancer. However, most ER-positive (ER+) metastatic breast cancers (MBC) eventually become resistant to these interventions. Interestingly, high dose estrogen can induce apoptosis in breast cancer cell lines, and high-dose estrogen has been used for over 50 years as therapy for ER+ breast cancer. The mechanism for growth control of MBC by high dose estrogen is unclear. We present a patient with metastatic breast cancer whose tumor was found to have amplification of ESR1 by tumor genome sequencing. This patient was treated with high dose estradiol and subsequently experienced a sustained partial response, which was predicted by prior experiments with patient-derived xenograft animal models containing breast cancers with ER amplification.



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Create a free account to continue reading this article.

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Karthik Kota

Internal Medicine, UPMC Presbyterian

For correspondence:
kotakj@upmc.edu

Adam Brufsky

Division of Hematology/Oncology, Magee Women's Hospital of UPMC

Steffi Oesterreich

Pharmacology and Chemical Biology, University Of Pittsburgh

Adrian Lee

Pharmacology and Chemical Biology, University Of Pittsburgh

Karthik Kota

Internal Medicine, UPMC Presbyterian

For correspondence:
kotakj@upmc.edu

Adam Brufsky

Division of Hematology/Oncology, Magee Women's Hospital of UPMC

Steffi Oesterreich

Pharmacology and Chemical Biology, University Of Pittsburgh

Adrian Lee

Pharmacology and Chemical Biology, University Of Pittsburgh