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BIOMARKER:

ER Y537N

i
Other names: ESR1, Era, ESR, NR3A1, ER, ER beta
Entrez ID:
1d
Proteomic profiling reveals that ESR1 mutations enhance cyclin-dependent kinase signaling. (PubMed, Sci Rep)
Additionally, protein expression and phosphorylation patterns, while under different regulation, still recapitulated the estrogen-independent phenotype of ER mutant cells. Our study is the first proteome-centric characterization of ESR1 mutant models, out of which we confirm estrogen independence of ER mutants and reveal the enrichment of immune signaling pathways at the proteomic level.
Journal
|
ER (Estrogen receptor) • mTOR (Mechanistic target of rapamycin kinase)
|
ER mutation • ER Y537S • ESR1 mutation • ER Y537N • ER expression
1m
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)
4ms
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)
5ms
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
5ms
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
5ms
Differential dynamics of fragmentomic and epigenetic circulating tumor DNA (ctDNA) features in first-line Palbociclib and Ribociclib treatment for Hormone Receptor (HR) positive, HER2 negative metastatic breast cancer (MBC) (SABCS 2023)
However, the lack of prospective cohorts comparing the distinctions among palbociclib (PAL), ribociclib (RIB) and abemaciclib (ABE) poses a significant clinical knowledge gap. Out of the 114 pts enrolled, 59 received PAL, 48 RIB, and 16 ABE. In the de novo subgroup, 51.4 % of pts were treated with PAL, 42.9% with RIB, and 5.7% with ABE. Among the pts who received PAL, 7 harbored an ESR1 mutation at BL (D538G: 2, H377R: 1, Y537N: 1, Y537S: 3).
Clinical • Circulating tumor DNA • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CDK4 (Cyclin-dependent kinase 4)
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HR positive • HER-2 negative • PIK3CA mutation • ER mutation • ER Y537S • ER D538G • ESR1 mutation • AKT1 mutation • ER Y537N • PTEN mutation + HR positive
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Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib)
5ms
ESR1 genomic alterations (GAs) and coexistent putative resistance alterations in comprehensive genomic profiling (CGP) of metastatic breast cancer (MBC) (SABCS 2023)
CGP detects a wide spectrum of mutations in ESR1, including missense and indel mutations and fusions. When LBx TF is < 1%, sensitivity for ESR1mut is reduced and repeat testing should be considered. ESR1mut can coexist with complementary or competing resistance mechanisms, particularly when ESR1 is a minor allele, which could impact benefit from novel ET approved for patients with ESR1 mutations.
Metastases
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCDC170(Coiled-Coil Domain Containing 170)
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HR positive • FGFR2 fusion • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N • ER-CCDC170 fusion • ER amplification
|
FoundationOne® Liquid CDx
5ms
Exploration of ctDNA Dynamics in the PACE Trial: A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab for HR+/HER2- Metastatic Breast Cancer (SABCS 2023)
Conclusions The PACE trial offers one of the largest clinical trial cohorts describing the genomic landscape of HR+/HER2- MBC post-CDK4/6 exposure. Results from this correlative study provide a comprehensive mutational landscape post-CDK4/6i, demonstrate associations between mutations and clinical outcomes, and suggest the potential value of early ctDNA dynamics in this setting.
P2 data • Clinical • PD(L)-1 Biomarker • Circulating tumor DNA • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • GATA3 (GATA binding protein 3)
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TP53 mutation • HER-2 negative • PIK3CA mutation • PTEN mutation • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N • CDK4 mutation
|
Guardant360® CDx
|
Ibrance (palbociclib) • Bavencio (avelumab) • fulvestrant
5ms
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
10ms
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
12ms
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)
over1year
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)
over1year
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
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ER (Estrogen receptor)
|
ER positive • ER mutation • ER Y537S • ER D538G • 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 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)
over1year
Exploratory subgroup and biomarker analyses of acelERA Breast Cancer: Phase II study of giredestrant (GDC-9545) vs physician’s choice of endocrine therapy for previously treated, estrogen receptor+, HER2– advanced breast cancer (SABCS 2022)
METHODS Patients were post- and pre- or peri-menopausal women, or men, with ER+, HER2– aBC who had progressed after 1–2 lines of systemic therapy in the advanced setting (≤1 targeted agent; ≤1 chemotherapy regimen; prior fulvestrant allowed). Overall, these data support continued investigation of giredestrant to advance and improve treatment outcomes in hormone receptor+ BC. Exploratory subgroup analyses
P2 data
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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PIK3CA mutation • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N
|
FoundationOne® Liquid CDx • PredicineCARE™
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fulvestrant • giredestrant (GDC-9545)
over1year
Estrogen receptor 1 (ESR1) mutations in circulating tumor DNA (ctDNA) from patients with ER+/HER2- metastatic breast cancer (mBC) treated with lasofoxifene or fulvestrant in the ELAINE 1 study (SABCS 2022)
Our data demonstrate that LAS more effectively decreased or cleared mutESR1 than Fulv. Further, mutESR1 clearance was associated with prolonged PFS and more CB in LAS but not Fulv pts, suggesting that LAS results in robust mutESR1 target engagement. Taken together, our data suggest mutESR1 as a potential liquid biomarker for predicting response to LAS in mutESR1, endocrine-resistant mBC pts.
Clinical • Circulating tumor DNA
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
HER-2 negative • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N
|
fulvestrant • Fablyn (lasofoxifene)
over1year
Estrogen receptor 1 (ESR1) mutations in circulating tumor DNA (ctDNA) from patients with ER+/HER2- metastatic breast cancer (mBC) treated with lasofoxifene plus abemaciclib in the ELAINE 2 study (SABCS 2022)
29 patients (median of 2 prior metastatic therapies: 97% CDK4/6i, 79% fulvestrant, 48% chemotherapy) had BL mutESR1 of Y537S (66%), D538G (45%), Y537N (28%), and other less frequently detected mutations; 14 (48.3%) patients were polyclonal. In ELAINE 2, 81% of patients had decrease/cleared (ND) mutESR1 after 4 wks of LAS plus Abema, which correlated with clinical benefit. All mutESR1 detected appear targeted with this therapy. High sensitivity and favorable PPV were observed in patients with decreased MAF, and even more so in those with ND MAF; however, increased MAF was less specific and not as predictive of treatment failure.
Clinical • Circulating tumor DNA
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
HER-2 negative • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N
|
Verzenio (abemaciclib) • fulvestrant • Fablyn (lasofoxifene)
over1year
Circulating tumor DNA genotyping of intrinsic and acquired gene alterations in patients with advanced breast cancer receiving the cyclin-dependent Kinase 4/6 inhibitor Palbociclib: Biomarker results from POLARIS (SABCS 2022)
Patients with mutated ESR1 and PIK3CA or CCND1 and FGFR1 amp at baseline had shorter rwPFS than patients with wild-type genes . Genotyping analysis of progression ctDNA highlights the emergence of mutations in estrogen receptor and cell cycle pathways under selective therapeutic pressure and could guide monitoring and therapeutic sequencing for patients with HR+/HER2– MBC.
Clinical • Circulating tumor DNA
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • CCND1 (Cyclin D1)
|
EGFR mutation • HR positive • HER-2 negative • PIK3CA mutation • ATM mutation • FGFR1 amplification • ER mutation • ER Y537S • ER D538G • ESR1 mutation • ER Y537N
|
Guardant360® CDx
|
Ibrance (palbociclib)
over1year
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
over1year
Interrogating breast cancer heterogeneity using single and pooled circulating tumor cell analysis. (PubMed, NPJ Breast Cancer)
Furthermore, de novo mutational signatures derived from CTCs described patient-specific biological processes. These data suggest that tumor tissue and CTCs provide complementary clinically relevant information to map tumor heterogeneity and tumor evolution.
Journal • Circulating Tumor Cells
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53)
|
HER-2 positive • TP53 mutation • ER positive • ER mutation • ESR1 mutation • ER Y537N
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 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)
2years
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
over2years
Esr1 hotspot mutations in circulating tumor DNA mutation are associated with endocrine therapy resistance in metastatic breast cancer (SABCS 2021)
Patients with HR+ MBC were evaluated before endocrine therapy (Anastrozole, Exemestane and Letrozole ) +/- CDK4/6 inhibitors (Palbociclib, Ribociclib, Abemaciclib), and every six months after initiation of therapy. The outcome of this study demonstrated that patients with mutations on known ESR1 hotspots (E380Q, L536H, Y537N/C/S and D538G) develop clinical resistance to endocrine therapy. Evaluation of these ESR1 hotspots mutations by ctDNA could be reliably used to monitor the response to endocrine therapy and predict the prognosis for MBC patients.
Circulating tumor DNA
|
ER (Estrogen receptor)
|
ER mutation • ER D538G • ER Y537N
|
Guardant360® CDx
|
Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • letrozole • anastrozole
over2years
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)
over2years
Clinical • P1/2 data
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
|
HER-2 negative • HER-2 mutation • ER mutation • ER Y537S • ER D538G • ER Y537N
|
Ibrance (palbociclib) • fulvestrant • amcenestrant (SAR439859)
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. | 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)
almost3years
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
3years
Mutation analysis using cell-free DNA for endocrine therapy in patients with HR+ metastatic breast cancer. (PubMed, Sci Rep)
Of those, 31 (41.3%) received letrozole with palbociclib, and 28 (37.3%) received exemestane and everolimus (EverX). In contrast, PIK3CA mutations were significantly associated with longer TTP in patients receiving EverX treatment (median TTP of EverX: 15.9 months vs. 5.2 months, p = 0.01) and remained a significant factor in multivariable analysis for TTP of EverX in this subgroup (hazard ratio = 0.2, 95% CI = 0.1- 0.8, p = 0.03). ESR1 and PIK3CA mutations in cfDNA were associated with clinical efficacies of ET in HR+ MBC patients.
Clinical • Journal
|
ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
|
PIK3CA mutation • PIK3CA H1047R • PIK3CA E545K • ER mutation • ER Y537S • ER D538G • PIK3CA E542K • ER Y537N • PIK3CA E545 • PIK3CA E542
|
Ibrance (palbociclib) • everolimus • letrozole • exemestane
3years
[VIRTUAL] Preclinical characterization of LY3484356, a novel, potent and orally bioavailable selective estrogen receptor degrader (SERD) (AACR 2021)
Fulvestrant, a pure antagonist and selective estrogen receptor degrader (SERD) is approved for the treatment of HR+/HER2- metastatic breast cancer. LY3484356 has shown synergy or additivity in combination with CDK4/6 inhibitor abemaciclib, mTOR inhibitor everolimus and PIK3CA inhibitor alpelisib in inhibiting cell proliferation in ER+ breast cancer cell lines in vitro and tumor growth inhibition in relevant xenograft or PDX models in vivo. The first-in-human Phase 1/2 clinical trial of LY3484356 (EMBER, ClinicalTrials.gov NCT04188548) is currently ongoing and a window-of-opportunity study evaluating the pharmacodynamic effects of LY3484356 in early stage breast cancer is expected to begin early 2021.
Preclinical
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
|
HER-2 negative • ER Y537S • ER Y537N
|
everolimus • Piqray (alpelisib) • Verzenio (abemaciclib) • fulvestrant • imlunestrant (LY3484356)
3years
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
over3years
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)
over3years
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
over3years
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)
over3years
P1/2 data • IO biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • BCL2 (B-cell CLL/lymphoma 2)
|
ER Y537S • ER D538G • BCL2 expression • ER Y537N
|
amcenestrant (SAR439859)
almost4years
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
almost4years
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)