^
Contact us  to learn more about
our Premium Content:  News alerts, weekly reports and conference planners
BIOMARKER:

ER mutation

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
1d
Giredestrant for Estrogen Receptor-Positive, HER2-Negative, Previously Treated Advanced Breast Cancer: Results From the Randomized, Phase II acelERA Breast Cancer Study. (PubMed, J Clin Oncol)
Although the acelERA BC study did not reach statistical significance for its primary INV-PFS end point, there was a consistent treatment effect with giredestrant across most key subgroups and a trend toward favorable benefit among patients with ESR1-mutated tumors. Giredestrant was well tolerated, with a safety profile comparable to PCET and consistent with known endocrine therapy risks. Overall, these data support the continued investigation of giredestrant in other studies.
P2 data • Journal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • HER-2 negative • ER mutation • ESR1 mutation • ER positive + HER-2 negative
|
fulvestrant • giredestrant (GDC-9545)
5d
Exemestane plus everolimus and palbociclib in metastatic breast cancer: clinical response and genomic/transcriptomic determinants of resistance in a phase I/II trial. (PubMed, Nat Commun)
Multi-omics data from the phase IIa patients (n = 24 tumor/17 blood biopsy exomes; n = 27 tumor transcriptomes) showed potential mechanisms of resistance (convergent evolution of HER2 activation, BRAFV600E), identified joint genomic/transcriptomic resistance features (ESR1 mutations, high estrogen receptor pathway activity, and a Luminal A/B subtype; ERBB2/BRAF mutations, high RTK/MAPK pathway activity, and a HER2-E subtype), and provided hypothesis-generating results suggesting that mTOR pathway activation correlates with response to the trial's therapy. Our results illustrate how genome and transcriptome sequencing may help better identify patients likely to respond to CDK4/6i therapies.
P1/2 data • Clinical Trial,Phase I • Clinical Trial,Phase II • Journal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor)
|
BRAF V600E • BRAF V600 • HER-2 mutation • ER mutation • ESR1 mutation
|
Ibrance (palbociclib) • everolimus • exemestane
23d
A circulating tumor fraction DNA biomarker response stratified by ESR1 mutation status correlates with overall survival in patients with HR+ HER2- metastatic breast cancer (AACR 2024)
Patients with ESR1m acquired on AI may retain treatment response if switched to selective estrogen receptor degraders (SERDs) like fulvestrant... xF Monitor is a ctDNA assay that tracks changes in quantitative ctDNA TF and simultaneously monitors for the emergence of ESR1m, providing a diagnostic that identifies resistance to AI therapy and enables early switch to therapies that could improve outcomes in a patient population with poor prognosis. A larger prospective clinical study is needed to validate these findings.
Clinical • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
HER-2 negative • ER mutation • ESR1 mutation
|
Tempus xF Assay • Tempus xF Monitor assay
|
fulvestrant
23d
Mutational Analysis of Circulating Tumor DNA in Patients With Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer Receiving Palbociclib: Results From the TREnd Trial. (PubMed, JCO Precis Oncol)
Mutations in ESR1 and in PI3K pathway genes at T0 were associated with worse prognosis in palbociclib-treated patients. We describe the emergence of newly acquired mutations in palbociclib-treated patients, which might potentially affect subsequent treatment.
Journal • Circulating tumor DNA • Metastases
|
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) • FGFR2 (Fibroblast growth factor receptor 2) • CDK4 (Cyclin-dependent kinase 4)
|
TP53 mutation • ER positive • HER-2 negative • PIK3CA mutation • FGFR2 mutation • ER mutation • ESR1 mutation • EGFR positive • CDK4 mutation
|
TruSight Tumor 170 Assay
|
Ibrance (palbociclib)
28d
Liver tropism of ER mutant breast cancer is characterized by unique molecular changes and immune infiltration. (PubMed, Breast Cancer Res Treat)
Our data provide a comprehensive characterization of the behaviors and mechanisms of ESR1 mutant liver metastasis, paving the way for the development of personalized therapy to target liver metastasis for patients with ESR1 mutant breast cancer.
Journal
|
ER (Estrogen receptor)
|
ER positive • ER mutation • ESR1 mutation
1m
CDK4/6i-treated HR+/HER2- breast cancer tumors show higher ESR1 mutation prevalence and more altered genomic landscape. (PubMed, NPJ Breast Cancer)
In conclusion, our work uncovers opportunities for further treatment personalization and stresses the need for effective combination treatments to address the altered tumor genomic landscape following AI+CDK4/6i exposure. Further, we demonstrated the potential of RWD for refining patient treatment strategy and guiding clinical trial design.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • CDK4 (Cyclin-dependent kinase 4)
|
HER-2 positive • HR positive • HER-2 negative • HER-2 mutation • ER mutation • ESR1 mutation • HR positive + HER-2 negative • PTEN mutation + HR positive
1m
Identifying prognostic biomarkers for palbociclib add-on therapy in fulvestrant-resistant breast cancer using cell-free DNA sequencing. (PubMed, ESMO Open)
Cancer panel testing for cfDNA identified prognostic and predictive biomarkers for palbociclib add-on therapy after acquiring fulvestrant resistance in patients with HR+/HER2- ABC/MBC.
Journal
|
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) • RUNX1 (RUNX Family Transcription Factor 1) • FOXA1 (Forkhead Box A1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
|
TP53 mutation • HR positive • HER-2 negative • PIK3CA mutation • ER mutation • AR mutation • ESR1 mutation • MAP3K1 mutation • FOXA1 mutation
|
Ibrance (palbociclib) • fulvestrant
1m
US Food and Drug Administration Approval Summary: Elacestrant for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, ESR1-Mutated Advanced or Metastatic Breast Cancer. (PubMed, J Clin Oncol)
The approval of elacestrant in ER+, HER2- advanced or metastatic breast cancer was restricted to patients with ESR1 mutations. Benefit-risk assessment in the ESR1-mut subgroup was favorable on the basis of a statistically significant improvement in PFS in the context of an acceptable safety profile including no evidence of a potential detriment in OS. By contrast, the benefit-risk assessment in patients without ESR1 mutations was not favorable. Elacestrant is the first oral estrogen receptor antagonist to receive FDA approval for patients with ESR1 mutations.
FDA event • Journal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • EGFR mutation • HER-2 negative • HER-2 mutation • ER mutation • ESR1 mutation • EGFR positive
|
Orserdu (elacestrant)
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)
1m
The clinical impact of plasma estrogen receptor-1 mutation in patients with metastatic breast cancer: A meta-analysis. (PubMed, Adv Clin Exp Med)
According to the findings of this meta-analysis, the assessment for plasma ESR1 mutations may provide prognostic and clinical guidance regarding subsequent endocrine therapy decisions for ER-positive, metastatic BC patients who had received prior therapy with AIs.
Retrospective data • Journal • Metastases
|
ER (Estrogen receptor)
|
ER positive • ER mutation • ER Y537S • ER D538G • ESR1 mutation
2ms
Vaccines targeting ESR1 activating mutations elicit anti-tumor immune responses and suppress estrogen signaling in therapy resistant ER+ breast cancer. (PubMed, Hum Vaccin Immunother)
We then show the presence of human T cells reactive to ESR1mut epitopes in an ER+ BC patient. These findings support the development of ESR1mut vaccines, which we are testing in a Phase I clinical trial.
Journal
|
ER (Estrogen receptor)
|
ER mutation • ESR1 mutation
2ms
Oral SERD, a Novel Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer. (PubMed, Cancers (Basel))
The first-generation selective estrogen receptor degrader (SERD) fulvestrant has shown some activity against ESR1 mutant tumors...Several oral SERDs are now in phase III trials for early and advanced ER+ breast cancer. This review summarizes the background of oral SERD development, the current status, and future perspectives.
Review • Journal
|
ER (Estrogen receptor)
|
ER positive • ER mutation • ESR1 mutation
|
fulvestrant
2ms
Estrogen Receptor Mutations as Novel Targets for Immunotherapy in Metastatic Estrogen Receptor-Positive Breast Cancer. (PubMed, Cancer Res Commun)
Ultimately, we identified five peptides derived from the three most common ESR1 mutations (D538G, Y537S, and E380Q) and their associated wild-type peptides, which were the most immunogenic. Overall, these data confirm the immunogenicity of epitopes derived from ESR1 and highlight the potential of these peptides to be targeted by novel immunotherapy strategies.
Journal • IO biomarker • Metastases
|
ER (Estrogen receptor)
|
ER positive • ER mutation • ER Y537S • ER D538G • ESR1 mutation
2ms
Concurrent Tissue and Circulating Tumor DNA Molecular Profiling to Detect Guideline-Based Targeted Mutations in a Multicancer Cohort. (PubMed, JAMA Netw Open)
This study suggests that unique actionable biomarkers are detected by both concurrent tissue and ctDNA testing, with higher ctDNA identification among patients with breast cancer. Integration of concurrent NGS testing into the routine management of advanced solid cancers may expand the delivery of molecularly guided therapy and improve patient outcomes.
Journal • Circulating tumor DNA
|
ER (Estrogen receptor)
|
ER mutation • ESR1 mutation
2ms
c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer. (PubMed, Breast Cancer Res)
Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2- mBC, highlighting the importance of integrated liquid biopsy.
Journal • Circulating tumor cells • Tumor cell • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • EPCAM (Epithelial cell adhesion molecule)
|
HER-2 positive • HR positive • HER-2 negative • PIK3CA mutation • MET overexpression • ER mutation • MET expression • ESR1 mutation • MET positive • HR positive + HER-2 negative • PTEN mutation + HR positive
2ms
Incongruity between T cell receptor recognition of breast cancer hotspot mutations ESR1 Y537S and D538G following exogenous peptide loading versus endogenous antigen processing. (PubMed, Cytotherapy)
To investigate the basis of this lack of recognition we performed immunopeptidomics analysis of a mutant-overexpressing lymphoblastoid cell line and found that the ESR1 Y537S neopeptide was not endogenously processed, despite binding to HLA-B*40:02 when exogenously pulsed onto the target cell. These results indicate that stimulation of T cells that likely derive from the naïve repertoire with pulsed minimal peptides may lead to the expansion of clones that recognize non-processed peptides, and highlights the importance of using methods that selectively expand T cells with specificity for antigens that are efficiently processed and presented.
Journal • IO biomarker
|
ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • IFNG (Interferon, gamma) • HLA-B (Major Histocompatibility Complex, Class I, B) • HLA-C (Major Histocompatibility Complex, Class I, C)
|
TP53 mutation • PIK3CA mutation • ER mutation • ER Y537S • ER D538G • ESR1 mutation • AKT1 mutation
3ms
Mechanisms of Endocrine Resistance in Hormone Receptor-Positive Breast Cancer. (PubMed, Cancer Treat Res)
Epigenetic changes, such as DNA methylation and histone modifications, can also contribute to ET resistance by altering the expression of genes that are involved in estrogen signaling. Understanding the mechanisms of resistance to ET is crucial for the development of new therapies that can overcome resistance and improve outcomes for patients with HR + BC.
Journal
|
ER (Estrogen receptor)
|
HR positive • ER mutation • ESR1 mutation
3ms
The value of oral selective estrogen receptor degraders in patients with HR-positive, HER2-negative advanced breast cancer after progression on ≥ 1 line of endocrine therapy: systematic review and meta-analysis. (PubMed, BMC Cancer)
The oral SERD regimen provides a significant PFS benefit compared to standard-of-care ET in patients with HR+/HER2- aBC after progression on ≥ 1 line of ET. In particular, we recommend oral SERDs as a preferred choice for those patients with ESR1m, and it could be a potential replacement for fulvestrant. The oral SERD regimen is also beneficial after progression on CDK4/6 inhibitors combined with endocrine therapy.
Retrospective data • Review • Journal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
HR positive • HER-2 negative • ER mutation • ESR1 mutation • PTEN mutation + HR positive
|
fulvestrant
3ms
Journal • Metastases
|
ER (Estrogen receptor)
|
ER positive • ER mutation • ESR1 mutation
|
Fablyn (lasofoxifene)
3ms
Palazestrant (OP-1250), a Complete Estrogen Receptor Antagonist, Inhibits Wild-type and Mutant ER-positive Breast Cancer Models as Monotherapy and in Combination. (PubMed, Mol Cancer Ther)
OP-1250 combines well with cyclin-dependent kinase 4 and 6 inhibitors in xenograft studies of ER+ breast cancer models and effectively shrinks intracranially implanted tumors, resulting in prolonged animal survival. With demonstrated preclinical efficacy exceeding fulvestrant in wild-type models, elacestrant in ESR1-mutant models, and tamoxifen in intracranial xenografts, OP-1250 has the potential to benefit patients with ER+ breast cancer.
Preclinical • Journal
|
ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4)
|
ER positive • ER mutation • ESR1 mutation
|
tamoxifen • fulvestrant • Orserdu (elacestrant) • palazestrant (OP-1250)
4ms
Phase classification
|
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 • ER mutation • ESR1 mutation
|
Orserdu (elacestrant) • samuraciclib (CT7001)
4ms
New P1/2 trial
|
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 • ER mutation • ESR1 mutation
|
Orserdu (elacestrant) • samuraciclib (CT7001)
4ms
SMARCB1-deficient sinonasal adenocarcinoma: a rare variant of SWI/SNF-deficient malignancy often misclassified as high-grade non-intestinal-type sinonasal adenocarcinoma or myoepithelial carcinoma. (PubMed, Virchows Arch)
The original diagnosis was usually high-grade non-intestinal-type adenocarcinoma or high-grade myoepithelial carcinoma. A correct diagnosis of these aggressive tumors could lead to improved targeted therapies with potentially better overall disease-specific survival.
Journal
|
ER (Estrogen receptor) • POLE (DNA Polymerase Epsilon) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • ARID1B (AT-Rich Interaction Domain 1B) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • PAX3 (Paired Box 3)
|
POLE mutation • ER mutation • ESR1 mutation • ARID1B mutation • SMARCB1 deletion • SMARCB1 mutation
4ms
Lasofoxifene versus fulvestrant for ER+/HER2- metastatic breast cancer with an ESR1 mutation: results from the randomized, phase II ELAINE 1 trial. (PubMed, Ann Oncol)
Lasofoxifene demonstrated encouraging antitumor activity versus fulvestrant and was well tolerated in patients with ESR1-mutated, endocrine-resistant mBC following progression on AI plus CDK4/6i. Consistent with target engagement, lasofoxifene reduced ESR1 MAF, and to a greater extent than fulvestrant. Lasofoxifene may be a promising targeted treatment for patients with ESR1-mutated mBC and warrants further investigation.
P2 data • Journal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
EGFR mutation • HER-2 negative • HER-2 mutation • ER mutation • ESR1 mutation
|
fulvestrant • Fablyn (lasofoxifene)
4ms
Open-label, phase II, multicenter study of lasofoxifene plus abemaciclib for treating women with metastatic ER+/HER2- breast cancer and an ESR1 mutation after disease progression on prior therapies: ELAINE 2. (PubMed, Ann Oncol)
Lasofoxifene plus abemaciclib had an acceptable safety profile, was well tolerated, and exhibited meaningful antitumor activity in women with ESR1-mutated, ER+/HER2- mBC after disease progression on prior CDK4/6i. Observed decreases in ESR1-mutant ctDNA with lasofoxifene concordant with clinical response suggest target engagement. If the ELAINE 2 findings are confirmed in the initiated, phase III, ELAINE 3 trial, these data could be practice-changing and help address a critical unmet need.
Clinical • P2 data • Journal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • EGFR mutation • HER-2 negative • HER-2 mutation • ER mutation • ESR1 mutation • CDK4 mutation
|
Verzenio (abemaciclib) • Fablyn (lasofoxifene)
4ms
Addressing unmet need in the management of patients with ER+/HER2-, ESR1-mutated metastatic breast cancer: clinician's perspective. (PubMed, Clin Adv Hematol Oncol)
For more than 20 years, fulvestrant (given as an intramuscular injection) was the only SERD approved by the US Food and Drug Administration for the treatment of ER+/HER2- metastatic breast cancer, and a standard second-line therapy following progression on an AI. This review discusses (1) the importance of routine testing for ESR1 mutations after disease recurrence or progression and the role of liquid biopsy in this regard; (2) elacestrant, a novel oral SERD approved in 2023 for the treatment of postmenopausal women and adult men with ER+/HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following 1 or more lines of endocrine therapy (unlike other SERDs, elacestrant is not associated with cardiac or ocular toxicity); and (3) new agents in development, including SERDs and innovative molecules targeting the ER-PROTACs, SERCAs, and CERANs-currently being tested in early-phase trials in combination with targeted agents, including CDK4/6 inhibitors.
Review • Journal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
HER-2 negative • HER-2 mutation • ER mutation • ESR1 mutation
|
fulvestrant • Orserdu (elacestrant)
4ms
Metastatic ER+ Breast Cancer: Mechanisms of Resistance and Future Therapeutic Approaches. (PubMed, Int J Mol Sci)
Despite progress in the development of molecularly targeted anticancer therapies, the emergence of resistance remains a major limitation and an area of unmet need. In this article, we review the mechanisms of acquired endocrine resistance in HR+ advanced breast cancer and discuss current and future investigational therapeutic approaches.
Review • Journal • Metastases
|
ER (Estrogen receptor)
|
HR positive • ER mutation • ESR1 mutation
4ms
ESR1 mutations in HR+/HER2-metastatic breast cancer: Enhancing the accuracy of ctDNA testing. (PubMed, Cancer Treat Rev)
Furthermore, we underscore the importance of detecting sub-clonal ESR1 mutations, as these variants can exert a pivotal influence on predicting both endocrine therapy resistance and responsiveness to SERDs. In essence, this work discusses the role of ctDNA analysis for detecting ESR1 mutations and their implications in tailoring effective therapeutic strategies for HR+/HER2- MBC.
Review • Journal • Circulating tumor DNA • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
HR positive • HER-2 negative • HER-2 mutation • ER mutation • ESR1 mutation
4ms
Assessment of early progression risk for patient with ESR1 mutations and hormone receptor positive (HR+)IHER2-negative metastatic breast cancer (MBC) (ABC 2023)
The first line HT was started with nonsteroidal AI (lertozole/anastrozole)... These findings suggest an increased risk of early progression (up to 1 year) among patients with ESR1 mutations who are taking AI as first-line therapy of (HR+)/HER2-negative MBC. Prospective studies are crucially important for further treatment tailoring, follow-up and cost-effectiveness assessment.
Clinical • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
HR positive • HER-2 negative • ER mutation • ESR1 mutation • HR positive + HER-2 negative
|
anastrozole
4ms
Liquid biopsy • Biopsy
|
ER (Estrogen receptor)
|
ER mutation • ESR1 mutation
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)
4ms
ERG Is a New Predisposition Gene for Bone Marrow Failure and Hematological Malignancy (ASH 2023)
Like the well-known disease genes GATA2 and RUNX1, ERG is also a member of the transcription factor heptad involved in HSC maintenance and differentiation. ERG adds to a growing list of genes whose unregulated expression contributes to HM and other cancers.Identification of causal germline ERG variants like those outlined in this study, has direct clinical implications for patient and family management including diagnosis, counselling, surveillance and treatment strategies such as selection of bone marrow transplant donors and potential for targeted therapies including gene and cell therapy.
Late-breaking abstract
|
RUNX1 (RUNX Family Transcription Factor 1) • ERG (ETS Transcription Factor ERG) • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor)
|
ER mutation • ERG overexpression
4ms
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
4ms
Mathematical modeling identifies optimum palbociclib-fulvestrant dose administration schedules for the treatment of estrogen receptor-positive breast cancer patients. (PubMed, Cancer Res Commun)
We found that continuous dosing of palbociclib is more effective for lowering overall tumor burden than the standard, pulsed-dose palbociclib treatment. Importantly, our mathematical modeling and statistical analysis platform provides a rational method for comparing treatment strategies in search of optimal combination dosing strategies of other cell-cycle inhibitors in ER+ breast cancer.
Journal
|
ER (Estrogen receptor)
|
ER positive • ER mutation • ER Y537S • ER expression
|
Ibrance (palbociclib) • fulvestrant
5ms
ESR1 Gene Mutations and Liquid Biopsy in ER-Positive Breast Cancers: A Small Step Forward, a Giant Leap for Personalization of Endocrine Therapy? (PubMed, Cancers (Basel))
Technically, several options exist, including Next Generation Sequencing and ultra-sensitive PCR-based techniques. In this context, personalization of ET through the surveillance of ESR1 mutations in the plasma of HR+ BC patients throughout the disease course represents an innovative way to improve the standard of care.
Review • Journal • Liquid biopsy • Biopsy
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
ER positive • HR positive • HER-2 negative • ER mutation • ESR1 mutation • ER expression
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
Phase Ia/b Study of Giredestrant ±Palbociclib and ±Luteinizing Hormone-releasing Hormone Agonists in Estrogen Receptor-positive, HER2-negative, Locally Advanced/Metastatic Breast Cancer. (PubMed, Clin Cancer Res)
Giredestrant was well tolerated and clinically active in patients who progressed on prior ET. Results warrant further evaluation of giredestrant in randomized trials in early- and late-stage ER+ breast cancer.
Journal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • HER-2 negative • ER mutation • ESR1 mutation • ER positive + HER-2 negative
|
Ibrance (palbociclib) • giredestrant (GDC-9545)
5ms
Crosstalk between adipocyte and tumor cells with ESR1 mutations via adipsin enhances tumor growth (SABCS 2023)
Combining C3aR inhibitors with fulvestrant or CDK4/6 inhibitors had a synergistic inhibitory effect on ESR1 mutant cells...Our findings suggest that upregulation of adipsin from ESR1 mutant cells and adipocytes in crosstalk increases tumor cell growth. Future studies will investigate the critical role of adipsin's auto- and paracrine effects in breast cancer with ESR1 mutations.
Tumor cell
|
ER (Estrogen receptor)
|
ER mutation • ER Y537S • ER D538G • ESR1 mutation
|
fulvestrant
5ms
Personalized circulating tumor DNA testing for recurrence detection and treatment response monitoring in patients with metastatic invasive lobular carcinoma (SABCS 2023)
At variant level, PIK3CA p.H1047R (22%) and RBM26 p.Q701Tfs*23 (10%) were the top two somatic variants identified...Conclusions ctDNA status and dynamics correlate well with clinical status of patients with mILC, as determined by conventional monitoring tools such as imaging and biopsy. Our results indicate that personalized, tumor-informed, longitudinal ctDNA testing may serve as a useful tool for detection of progression and monitoring treatment response in mILC patients.
Clinical • Circulating tumor DNA • Metastases
|
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) • CDH1 (Cadherin 1) • IGF1 (Insulin-like growth factor 1)
|
TP53 mutation • PIK3CA mutation • PIK3CA H1047R • ER mutation • ESR1 mutation
|
Signatera™
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
ESR1 mutations emerging during neoadjuvant endocrine therapy in postmenopausal ER+/HER2- early breast cancer patients: prevalence and prognostic impact (SABCS 2023)
Most patients were treated with aromatase inhibitors (n=107, 75.9%), while 24.1% (n=34) received tamoxifen...Although the limited sample size of our study did not allow reaching statistical significance, our results suggest, for the first time, worse survival outcomes for patients with a ESR1mut detected in post-NET primary tumors. The role of next-generation oral SERDs as neoadjuvant or adjuvant endocrine therapy to prevent ESR1mut-related relapses remains to be determined.
Clinical
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
HER-2 negative • ER mutation • ESR1 mutation
|
tamoxifen