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    BIOMARKER:

    ER Y537C

    i
    Other names: ESR1, Era, ESR, NR3A1, ER, ER beta
    Entrez ID:
    2099
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    5ms
    ELAINE 1: Evaluation of Lasofoxifene Versus Fulvestrant in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (clinicaltrials.gov)
    P2, N=100, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Feb 2024 --> Dec 2024 | Trial primary completion date: Feb 2024 --> Dec 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N • ER L536Q • ER Y537C
    |
    fulvestrant • Fablyn (lasofoxifene)
    7ms
    ELAINEII: Evaluation of Lasofoxifene Combined With Abemaciclib in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (clinicaltrials.gov)
    P2, N=29, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Jan 2024 --> May 2024 | Trial primary completion date: Jan 2024 --> May 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N • ER L536Q • ER Y537C
    |
    Verzenio (abemaciclib) • Fablyn (lasofoxifene)
    9ms
    Exploring the spatial landscape of the Estrogen Receptor proximal proteome with antibody-based proximity labeling. (PubMed, Mol Cell Proteomics)
    These include proteins involved in highly dynamic processes such as sumoylation and ubiquitination difficult to detect with traditional protein interaction approaches. Overall, we present BAR as an effective approach to investigate the ERα proximal proteome in a spatial context and demonstrate its application in different experimental conditions.
    Journal
    |
    ER (Estrogen receptor)
    |
    ER positive • ER Y537C
    10ms
    ELAINEII: Evaluation of Lasofoxifene Combined With Abemaciclib in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (clinicaltrials.gov)
    P2, N=29, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Feb 2023 --> Jan 2024 | Trial primary completion date: Feb 2023 --> Jan 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N • ER L536Q • ER Y537C
    |
    Verzenio (abemaciclib) • Fablyn (lasofoxifene)
    10ms
    ESR1 F404 mutations and acquired resistance to fulvestrant in ESR1 mutant breast cancer. (PubMed, Cancer Discov)
    Several oral ERa degraders were active against compound mutant models. We have identified a resistance mechanism specific to fulvestrant, that can be targeted by treatments in clinical development.
    Preclinical • Journal
    |
    ER (Estrogen receptor)
    |
    HR positive • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER F404L • ER Y537C
    |
    fulvestrant
    10ms
    Clinical relevance of circulating ESR1 mutations during endocrine therapy for advanced hormone-dependent endometrial carcinoma. (PubMed, BMC Cancer)
    ESR1 mutations do not seem to be involved in the mechanisms of resistance to AI or M in HR+ endometrial cancer. The clinical relevance of their detection is not demonstrated.
    Retrospective data • Journal • Metastases
    |
    ER (Estrogen receptor)
    |
    ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N • ER Y537C
    |
    megestrol
    11ms
    Design and Development of the APIS ESR1 Mutations Kit to Detect Eleven Mutations Relevant to Acquired Endocrine Therapy Resistance (SABCS 2023)
    The ESR1 Mutations Kit demonstrated high sensitivity and performance as a qualitative qPCR assay to detect eleven ESR1 mutations. Mutations detected with the APIS ESR1 Mutations Kit
    ER (Estrogen receptor) • KIT (KIT proto-oncogene, receptor tyrosine kinase)
    |
    TP53 mutation • ER positive • KIT mutation • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N • ER L536Q • ER Y537C
    |
    APIS ESR1 Mutations Kit
    11ms
    The Design and Development of the APIS ESR1 Mutations Kit to Detect Eleven Mutations Relevant to Acquired Endocrine Therapy Resistance. (AMP 2023)
    The APIS ESR1 Mutations Kit demonstrated high sensitivity and performance as a qualitative qPCR assay to detect 11 ESR1 mutations.
    ER (Estrogen receptor) • KIT (KIT proto-oncogene, receptor tyrosine kinase)
    |
    TP53 mutation • KIT mutation • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N • ER L536Q • ER Y537C
    |
    APIS ESR1 Mutations Kit
    over1year
    Development of sensitive and robust multiplex digital PCR assays for the detection of ESR1 mutations in the plasma of metastatic breast cancer patients. (PubMed, Clin Chim Acta)
    Our assays have proven to be robust and highly sensitive and are very well-suited for monitoring ESR1 mutations in the plasma of MBC patients.
    Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N • ER Y537C
    over1year
    ELAINE 1: Evaluation of Lasofoxifene Versus Fulvestrant in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (clinicaltrials.gov)
    P2, N=100, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Feb 2023 --> Feb 2024 | Trial primary completion date: Feb 2023 --> Feb 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N • ER L536Q • ER Y537C
    |
    fulvestrant • Fablyn (lasofoxifene)
    almost2years
    ELAINEII: Evaluation of Lasofoxifene Combined With Abemaciclib in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (clinicaltrials.gov)
    P2, N=29, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Nov 2022 --> Feb 2023 | Trial primary completion date: Nov 2022 --> Feb 2023
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N • ER L536Q • ER Y537C
    |
    Verzenio (abemaciclib) • Fablyn (lasofoxifene)
    almost2years
    Genome engineering for estrogen receptor mutations reveals differential responses to anti-estrogens and new prognostic gene signatures for breast cancer. (PubMed, Oncogene)
    Differential gene expression analysis demonstrates up-regulation of estrogen-responsive genes, as expected, but also reveals that enrichment for interferon-regulated gene expression is a common feature of all mutations. Finally, a new gene signature developed from the gene expression profiles in ER mutant cells predicts clinical response in breast cancer patients with ER mutations.
    Journal • Gene Signature
    |
    ER (Estrogen receptor)
    |
    ER positive • ER mutation • ER Y537S • ER D538G • ER Y537N • ER Y537C
    almost2years
    ELAINE 1: Evaluation of Lasofoxifene Versus Fulvestrant in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (clinicaltrials.gov)
    P2, N=100, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Feb 2022 --> Feb 2023 | Trial primary completion date: Feb 2022 --> Feb 2023
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N • ER L536Q • ER Y537C
    |
    fulvestrant • Fablyn (lasofoxifene)
    2years
    Clinical relevance of circulating ESR1 mutations during endocrine therapy for advanced hormone-dependent endometrial carcinoma (ESGO 2022)
    The aim of this study was to explore the incidence of circulating ESR1 mutations in patients treated by AA or megestrol acetate (M) for advanced endometrial carcinoma.Methodology: This single-center retrospective study was performed at the Henri Becquerel Center (Rouen) and looked for circulating ESR1 gene mutations by droplet digital PCR (E380Q, L536R, Y537S, Y537N, Y537C, D538G, S463P) in patients with advanced HR+ endometrial carcinoma treated between 2008 and 2020 for at least 30 days by AA or M. Timepoints were before exposure and at progression/during endocrine therapy. 22 patients were included: 13 were treated with AA, 12 of whom progressed; 9 patients were treated with M, 8 of whom progressed... ESR1 mutations do not seem to be involved in the mechanisms of resistance to AA or M in HR+ endometrial cancer. The clinical relevance of their detection is not demonstrated.
    Clinical
    |
    ER (Estrogen receptor)
    |
    ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N • ER Y537C
    |
    megestrol
    over2years
    ELAINEII: Evaluation of Lasofoxifene Combined With Abemaciclib in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (clinicaltrials.gov)
    P2, N=29, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial primary completion date: May 2022 --> Nov 2022
    Trial primary completion date • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N • ER L536Q • ER Y537C
    |
    Verzenio (abemaciclib) • Fablyn (lasofoxifene)
    over2years
    ESR1 F404 mutations and acquired resistance to fulvestrant in the plasmaMATCH study. (ASCO 2022)
    We have identified a novel resistance mechanism to fulvestrant, with F404 mutations acquired in patients with pre-existing activating ESR1 mutations. F404 confers fulvestrant resistance through the loss of a pi-stacking bond and likely reduced fulvestrant binding affinity, identifying a new potential target to overcome endocrine therapy resistance.
    Preclinical • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog)
    |
    BRCA2 mutation • BRCA1 mutation • HR positive • BRAF mutation • PIK3CA mutation • PTEN mutation • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER expression • ER F404L • ER Y537C
    |
    Guardant360® CDx
    |
    fulvestrant
    over2years
    Development and analytical validation of a highly sensitive and specific NAPA assay for the detection of ESR1mutations in circulating tumor cells and plasma circulating tumor DNA (AACR 2022)
    We present a low cost, highly specific, sensitive and robust assay for blood-based ESR1 profiling. The developed assay is fast, with a comparable sensitivity to ddPCR but has lower cost relative to ddPCR, and thus can be used as a fast screening method to classify patients as positive or negative for ESR1 mutations. Our results are consistent with reports that indicate that ESR1 mutations (especially D538G, Y537S) are associated with more aggressive disease.
    Circulating Tumor Cells • BRCA Biomarker • Circulating tumor DNA
    |
    ER (Estrogen receptor) • EPCAM (Epithelial cell adhesion molecule)
    |
    ER positive • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N • ER Y537C
    3years
    Evaluation of Lasofoxifene Versus Fulvestrant in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (clinicaltrials.gov)
    P2, N=100, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Recruiting --> Active, not recruiting
    Clinical • Enrollment closed
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative • ER mutation • ER Y537S • ER D538G • ER Y537N • ER L536Q • ER Y537C
    |
    fulvestrant • Fablyn (lasofoxifene)
    3years
    ELAINEII: Evaluation of Lasofoxifene Combined With Abemaciclib in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (clinicaltrials.gov)
    P2, N=29, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative • ER mutation • ER Y537S • ER D538G • ER Y537N • ER L536Q • ER Y537C
    |
    Verzenio (abemaciclib) • Fablyn (lasofoxifene)
    over3years
    ESR1 Gene Mutation in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Patients: Concordance Between Tumor Tissue and Circulating Tumor DNA Analysis. (PubMed, Front Oncol)
    The total concordance rate between ESR1 status on tumor tissue and plasma was 91%. Our results confirm the potential role of liquid biopsy as a non-invasive alternative to tissue biopsy for ESR1 mutation assessment in mBC patients.
    Clinical • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 positive • HR positive • HER-2 negative • ER mutation • ER Y537S • ER D538G • ER Y537N • HR positive + HER-2 negative • ER Y537C
    over3years
    ESR1 NAPA Assay: Development and Analytical Validation of a Highly Sensitive and Specific Blood-Based Assay for the Detection of ESR1 Mutations in Liquid Biopsies. (PubMed, Cancers (Basel))
    We present a low cost, highly specific, sensitive and robust assay for blood-based ESR1 profiling. The clinical performance of the ESR1 NAPA assay will be prospectively evaluated in a large number of well-characterized patient cohorts.
    Journal • BRCA Biomarker
    |
    ER (Estrogen receptor) • EPCAM (Epithelial cell adhesion molecule)
    |
    ER positive • ER mutation • ER Y537S • ER D538G • ER Y537N • ER Y537C
    almost4years
    Evaluation of Lasofoxifene Versus Fulvestrant in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (clinicaltrials.gov)
    P2, N=100, Recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Sep 2020 --> Feb 2022 | Trial primary completion date: Jul 2020 --> Feb 2022
    Clinical • Trial completion date • Trial primary completion date • Circulating tumor DNA
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative • ER mutation • ER Y537S • ER D538G • ER Y537N • ER L536Q • ER Y537C
    |
    fulvestrant • Fablyn (lasofoxifene)
    almost4years
    A single droplet digital PCR for ESR1 activating mutations detection in plasma. (PubMed, Oncogene)
    Furthermore, the monitoring of circulating tumor DNA using this technique during treatment follow-up predicts the clinical benefit of palbociclib-fulvestrant. The multiplex ESR1-ddPCR detects, in a single reaction, the most frequent ESR1 activating mutations with good sensitivity. This method allows real-time liquid biopsy for ESR1 mutation monitoring in large cohorts of patients.
    Journal
    |
    ER (Estrogen receptor)
    |
    ER mutation • ER Y537S • ER D538G • ER Y537N • ER Y537C
    |
    Ibrance (palbociclib) • fulvestrant
    almost4years
    ELAINEII: Evaluation of Lasofoxifene Combined With Abemaciclib in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (clinicaltrials.gov)
    P2, N=24, Recruiting, Sermonix Pharmaceuticals Inc. | Not yet recruiting --> Recruiting | Initiation date: Jul 2020 --> Sep 2020
    Clinical • Enrollment open • Trial initiation date • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative • ER mutation • ER Y537S • ER D538G • ER Y537N • ER L536Q • ER Y537C
    |
    Verzenio (abemaciclib) • Fablyn (lasofoxifene)
    4years
    Circulating Estrogen Receptor Mutations and Splice Variants in Advanced Prostate Cancer. (PubMed, BJU Int)
    ER mutations are detectable in plasma from patients with advanced prostate cancer. ER splice variants are frequently detected in both men with and without prostate cancer.
    Journal
    |
    ER (Estrogen receptor)
    |
    ER mutation • ER Y537S • ER D538G • ER Y537N • ER L536Q • ER Y537C
    over4years
    ELAINEII: Evaluation of Lasofoxifene Combined With Abemaciclib in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (clinicaltrials.gov)
    P2, N=24, Not yet recruiting, Sermonix Pharmaceuticals Inc.
    Clinical • New P2 trial • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 negative • ER mutation • ER Y537S • ER D538G • ER Y537N • ER L536Q • ER Y537C
    |
    Verzenio (abemaciclib) • Fablyn (lasofoxifene)
    over4years
    F-Fluoroestradiol Positron Emission Tomography Imaging of Activating Estrogen Receptor Alpha Mutations in Breast Cancer. (PubMed, J Nucl Med)
    Comparable F-FES uptake between Y537S-, Y537C-, and WT-ER xenografts was also observed using a 10-fold lower injected dose with the tissue biodistribution assay. Since tumoral uptake of F-FES is not significantly impacted by Y537S or Y537C ER mutations, the potential diagnostic utility of F-FES PET imaging is expected to be equally valid for patients with or without these activating ESR1 mutations.
    Journal
    |
    ER (Estrogen receptor)
    |
    ER mutation • ER Y537S • ER Y537C