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Selective Estrogen Receptor Degraders (SERDs)

  • Review
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Abstract

Purpose of Review

Update on the most recent clinical evidence on selective estrogen receptor degraders (SERDs) in the treatment of hormone receptor (HR)-positive (HR +), human epidermal growth factor receptor 2 (HER2)-negative (HER2-) breast cancer.

Recent Findings

Despite effective endocrine therapies, resistance commonly develops during treatment of HR + breast cancer and mutations in ESR1 account for a large proportion of resistance mechanisms. After demonstration of the superior efficacy of fulvestrant in ESR1-mutated tumors, recent advances allowed the development of a novel class of orally bioavailable selective estrogen receptor degraders (SERDs), which are beginning to revolutionize the field. The first approved oral SERD, elacestrant, is currently used in the second-line treatment of HR + /HER2- metastatic breast cancer, and a number of other oral SERDs are undergoing clinical evaluation in both the metastatic and early-stage settings.

Summary

SERDs are a rapidly developing class of antiestrogens that show activity in treatment of tumors harboring ESR1 mutations associated with resistance to earlier generations of endocrine therapy, but knowledge gaps remain, and further research is necessary to better define their optimal use.

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Authors and Affiliations

  1. Section of Medical Oncology, Yale University School of Medicine and Yale Cancer Center, New Haven, CT, USA

    Melissa Taylor & Adriana Kahn

  2. Division of Hematology/Oncology, University of Pittsburgh School of Medicine and UPMC Hillman Cancer Center, 300 Halket Street, Suite 3524, Pittsburgh, PA, 15213, USA

    Julia Foldi

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M.T. and A.K. prepared the initial draft of the manuscript text and tables 1-2. J.F. edited and finalized manuscript text and tables and prepared figure 1. All authors reviewed the final manuscript.

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Correspondence to Julia Foldi.

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Dr. Foldi reports personal fees from OncLive, personal fees from Research To Practice Inc., outside the submitted work; and has received research funding (paid to her institution) from Conquer Cancer/ASCO Foundation and the Pennsylvania Breast Cancer Coalition. The other authors declare that they have no conflicts of interest.

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Taylor, M., Kahn, A. & Foldi, J. Selective Estrogen Receptor Degraders (SERDs). Curr Breast Cancer Rep 16, 402–416 (2024). https://doi.org/10.1007/s12609-024-00563-0

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