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    BIOMARKER:

    HER-2 negative + ER positive + ESR1 mutation

    i
    Other names: ERBB2, CD340, HER-2, HER2, NEU, NGL, V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2
    Entrez ID:
    2064
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    Associations

    News

    Trials
    21d
    Real-World Outcomes of Elacestrant in ER+, HER2-, ESR1-mutant Metastatic Breast Cancer. (PubMed, Clin Cancer Res)
    Elacestrant demonstrated durable benefit in real-world clinical practice, particularly in earlier lines and in patients with prolonged prior ET exposure. Despite coexisting ESR1 and PI3K-pathway mutations, TTNT remained clinically meaningful, reinforcing the role of elacestrant in personalized ET sequencing strategies prior to chemotherapy, antibody-drug conjugates, or targeted combinations.
    Journal • Real-world evidence
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4)
    |
    ER positive • HER-2 negative • ESR1 mutation • HER-2 negative + ER positive • HER-2 negative + ER positive + ESR1 mutation
    |
    fulvestrant • Orserdu (elacestrant)
    2ms
    A Study to Evaluate Efficacy and Safety of Giredestrant Compared With Fulvestrant (Plus a CDK4/6 Inhibitor), in Participants With ER-Positive, HER2-Negative Advanced Breast Cancer Resistant to Adjuvant Endocrine Therapy (pionERA Breast Cancer) (clinicaltrials.gov)
    P3, N=1050, Recruiting, Hoffmann-La Roche | Trial primary completion date: Jul 2026 --> Feb 2027
    Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4)
    |
    ER positive • HER-2 negative • ESR1 mutation • HER-2 negative + ER positive • HER-2 negative + ER positive + ESR1 mutation
    |
    FoundationOne® Liquid CDx
    |
    Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • fulvestrant • giredestrant (RG6171)
    4ms
    A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With the Physician's Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer) (clinicaltrials.gov)
    P3, N=373, Active, not recruiting, Genentech, Inc. | Trial primary completion date: Oct 2026 --> Jul 2025
    Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ESR1 mutation • HER-2 negative + ER positive • HER-2 negative + ER positive + ESR1 mutation
    |
    everolimus • tamoxifen • fulvestrant • exemestane • giredestrant (RG6171)
    6ms
    Phase I study of H3B-6545 in patients with estrogen receptor-positive breast cancer. (PubMed, ESMO Open)
    H3B-6545 at 450 mg QD was tolerated and showed preliminary antitumor effects in Japanese patients with ER-positive, HER2-negative mBC, particularly for those with ESR1 mutations.
    P1 data • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ESR1 mutation • EGFR positive • HER-2 negative + ER positive • HER-2 negative + ER positive + ESR1 mutation
    |
    fulvestrant • H3B-6545
    6ms
    Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer. (PubMed, N Engl J Med)
    Among patients with ER-positive, HER2-negative advanced breast cancer, vepdegestrant was associated with significantly longer progression-free survival than fulvestrant in the subgroup with ESR1 mutations but not in the full patient population. (Funded by Pfizer and Arvinas Estrogen Receptor; VERITAC-2 ClinicalTrials.gov number, NCT05654623.).
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4)
    |
    ER positive • HER-2 negative • ESR1 mutation • EGFR positive • HER-2 negative + ER positive • HER-2 negative + ER positive + ESR1 mutation
    |
    fulvestrant • vepdegestrant (ARV-471)
    6ms
    First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer. (PubMed, N Engl J Med)
    In patients with ER-positive, HER2-negative advanced breast cancer with an ESR1 mutation that emerged during treatment, those who were switched to camizestrant with continuation of a CDK4/6 inhibitor during first-line therapy had significantly longer progression-free survival than those who maintained the aromatase-inhibitor combination. (Funded by AstraZeneca; SERENA-6 ClinicalTrials.gov number, NCT04964934.).
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ESR1 mutation • EGFR positive • HER-2 negative + ER positive • HER-2 negative + ER positive + ESR1 mutation
    |
    Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • camizestrant (AZD9833)
    6ms
    Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6) (clinicaltrials.gov)
    P3, N=315, Active, not recruiting, AstraZeneca | Trial primary completion date: Apr 2025 --> Jul 2025
    Trial primary completion date • Circulating tumor DNA
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HR positive • HER-2 negative • ESR1 mutation • HR positive + HER-2 negative • HER-2 negative + ER positive • HER-2 negative + ER positive + ESR1 mutation • HER-2 negative + HR positive + ESR1 mutation
    |
    Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • letrozole • anastrozole • camizestrant (AZD9833)
    8ms
    A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With the Physician's Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer) (clinicaltrials.gov)
    P3, N=320, Active, not recruiting, Genentech, Inc. | Trial completion date: Mar 2026 --> Oct 2026 | Trial primary completion date: Mar 2026 --> Oct 2026
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ESR1 mutation • HER-2 negative + ER positive • HER-2 negative + ER positive + ESR1 mutation
    |
    everolimus • tamoxifen • fulvestrant • exemestane • giredestrant (RG6171)
    10ms
    SUMIT-ELA: A Study of Samuraciclib and Elacestrant in Participants with Metastatic or Locally Advanced HR+/HER2-negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=49, Active, not recruiting, Carrick Therapeutics Limited | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • CDK4 (Cyclin-dependent kinase 4)
    |
    TP53 mutation • ER positive • HER-2 negative • HER-2 negative + ER positive • HER-2 negative + ER positive + ESR1 mutation
    |
    Orserdu (elacestrant) • samuraciclib (CT7001)
    12ms
    Imlunestrant with or without Abemaciclib in Advanced Breast Cancer. (PubMed, N Engl J Med)
    Among patients with ER-positive, HER2-negative advanced breast cancer, treatment with imlunestrant led to significantly longer progression-free survival than standard therapy among those with ESR1 mutations but not in the overall population. Imlunestrant-abemaciclib significantly improved progression-free survival as compared with imlunestrant, regardless of ESR1-mutation status. (Funded by Eli Lilly; EMBER-3 ClinicalTrials.gov number, NCT04975308.).
    Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    ER positive • HER-2 negative • ER mutation • EGFR positive • HER-2 negative + ER positive • HER-2 negative + ER positive + ESR1 mutation
    |
    Verzenio (abemaciclib) • Inluriyo (imlunestrant)
    1year
    A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With the Physician's Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer) (clinicaltrials.gov)
    P3, N=320, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Oct 2024 --> Mar 2026
    Enrollment closed • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative • ESR1 mutation • HER-2 negative + ER positive • HER-2 negative + ER positive + ESR1 mutation
    |
    everolimus • tamoxifen • fulvestrant • exemestane • giredestrant (RG6171)
    1year
    Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6) (clinicaltrials.gov)
    P3, N=312, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting
    Enrollment closed • Circulating tumor DNA
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HR positive • HER-2 negative • ER mutation • ESR1 mutation • HR positive + HER-2 negative • PTEN mutation + HR positive • HER-2 negative + ER positive • HER-2 negative + ER positive + ESR1 mutation • HER-2 negative + HR positive + ESR1 mutation
    |
    Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • letrozole • anastrozole • camizestrant (AZD9833)