^
1d
Efficiency of Fulvestrant Monotherapy After CDK4/6 Inhibitor Exposure: Is This a Viable Choice? (PubMed, Cancers (Basel))
Factors affecting the efficacy of fulvestrant monotherapy in second-line therapy include prior treatments, treatment duration, and genetic mutations. Given that the efficacy of fulvestrant was short-lived in the second or subsequent lines, participating in clinical trials is a vital option until a novel alternative treatment choice becomes available.
Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HR positive • HER-2 negative • HR positive + HER-2 negative
|
fulvestrant
3d
Post-marketing safety of elacestrant in breast cancer: a pharmacovigilance investigation using the FDA adverse event reporting system. (PubMed, BMC Pharmacol Toxicol)
FAERS data analyses were conducted to evaluate the safety of post-marketing clinical use of elacestrant and to ensure that physicians identify the risk factors for the AEs of this drug.
P4 data • Journal • Adverse events
|
ER (Estrogen receptor)
|
Orserdu (elacestrant)
3d
Design, synthesis, and biological evaluation of novel PROTACs compounds with good ERα degradation ability. (PubMed, Bioorg Med Chem)
And compared with fulvestrant, QDE-003-W exhibited more favorable pharmacokinetic (PK) characteristics. No significant adverse side effects were observed under the administration protocol, which indicates that the tested mice had excellent tolerance to both the administration method and the dosage. Such favorable PK characteristics and safety features further enhance the prospects of QDE-003-W as a viable candidate for subsequent preclinical and clinical development.
Journal
|
ER (Estrogen receptor)
|
fulvestrant
5d
Case report of stage IIIC low-grade serous ovarian cancer in a 13-year-old female treated with novel therapy. (PubMed, Gynecol Oncol Rep)
Given the tumor's limited sensitivity to chemotherapy, she was treated with neoadjuvant endocrine therapy (ET) using fulvestrant, palbociclib, and leuprolide. This case supports the potential role of endocrine-based targeted therapy in managing pediatric LGSOC, offering a viable alternative for patients with limited treatment options. Further research is needed to optimize treatment strategies and improve survival outcomes in this rare population.
Journal
|
ER (Estrogen receptor) • MUC16 (Mucin 16, Cell Surface Associated)
|
Ibrance (palbociclib) • fulvestrant • leuprolide acetate for depot suspension
5d
Evaluation of estrogenic and anti-estrogenic activity of endocrine disruptors using breast cancer spheroids: a comparative study of T47D and MCF7 cell lines in 2D and 3D models. (PubMed, Front Toxicol)
The in vitro model system was used to test the plasticizer Bisphenol A (BPA), a known endocrine disruptor (EDs) with estrogen-like action, aga inst 17β-Estradiol (E2), the endogenous nuclear estrogen receptor (nERs) ligand, and the anti-estrogenic drug Fulvestrant (FUL)...Through the use of these in vitro model systems - 2D and especially 3D, the latter of which allow better emulation of complex physiological and pathological processes occurring in vivo, the effects caused by EDs on nERs pathways can be detected and studied under various conditions. This approach performs as a preliminary screening tool to identify estrogenic substances, offering the potential to reduce reliance on in vivo experiments and contributing to improved environmental and health risk assessments.
Preclinical • Journal
|
ER (Estrogen receptor) • TGFB1 (Transforming Growth Factor Beta 1)
|
ER positive
|
fulvestrant
5d
Lipid metabolic reprogramming drives triglyceride storage and variable sensitivity to FASN inhibition in endocrine-resistant breast cancer cells. (PubMed, Breast Cancer Res)
Endocrine resistant breast cancer cells undergo a metabolic shift toward increased triglyceride storage and PUFAs with high degrees of desaturation. While TVB-2640 reduced lipid storage in most conditions, it had limited effects on the growth of endocrine resistant breast cancer cells. Targeting specific lipid metabolic dependencies, particularly pathways that produce PUFAs, represents a potential therapeutic strategy in endocrine resistant breast cancer.
Journal
|
ER (Estrogen receptor)
|
ER positive
|
tamoxifen • fulvestrant • denifanstat (TVB-2640)
11d
Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • EGFR positive
|
paclitaxel • docetaxel • tamoxifen • giredestrant (GDC-9545) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
12d
A Study of LY3484356 in Chinese Participants With Advanced Breast Cancer (clinicaltrials.gov)
P1, N=17, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2025 --> Dec 2026
Trial completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
HER-2 negative
|
Inluriyo (imlunestrant)
15d
CAMBRIA-1 & CAMBRIA-2 phase III trials: camizestrant versus standard endocrine therapy in ER+/HER2- early breast cancer. (PubMed, Future Oncol)
CAMBRIA-1 and CAMBRIA-2 are comparing the next-generation oral SERD camizestrant versus standard-of-care endocrine therapy (aromatase inhibitors or tamoxifen) in patients with ER-positive/HER2-negative early breast cancer, who are at intermediate or high risk of disease recurrence...CAMBRIA-2 is comparing 7 years of upfront adjuvant camizestrant versus endocrine therapy, with abemaciclib permitted in both treatment arms for the first 2 years. The primary endpoint for both studies is invasive breast cancer-free survival. Secondary endpoints include invasive disease-free survival, distant recurrence-free survival, overall survival, pharmacokinetics, patient-reported outcomes, safety and tolerability.Tweetable abstract: CAMBRIA-1 and CAMBRIA-2 are ongoing, randomized, open-label trials of adjuvant camizestrant, either as an upfront treatment or as a treatment after standard endocrine therapy, in patients with HR+/HER2- early breast cancer at intermediate to high risk of disease recurrence.Clinical Trial Registration: NCT05774951 (CAMBRIA-1); NCT05952557 (CAMBRIA-2).
P3 data • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
HER-2 positive • ER positive • HER-2 negative • EGFR positive • ER positive + HER-2 negative • HER-2 negative + ER positive
|
tamoxifen • Verzenio (abemaciclib) • camizestrant (AZD9833)
15d
GO39932: A Study of GDC-9545 Alone or in Combination With Palbociclib and/or Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer (clinicaltrials.gov)
P1, N=181, Active, not recruiting, Genentech, Inc. | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026
Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
HER-2 positive • ER positive • HER-2 negative • ER positive + HER-2 negative • HER-2 negative + ER positive
|
Ibrance (palbociclib) • triptorelin • goserelin acetate • giredestrant (GDC-9545)
16d
Enrollment change
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
HER-2 negative
|
tamoxifen • letrozole • anastrozole • exemestane • Inluriyo (imlunestrant)
16d
Journal
|
ER (Estrogen receptor)
18d
Elacestrant in hormone receptor-positive metastatic breast cancer: a post-hoc analysis. (PubMed, Explor Target Antitumor Ther)
Elacestrant shows promise for improving outcomes in hormone receptor-positive metastatic breast cancer, but further research is needed to confirm its effectiveness. Future studies should include larger sample sizes, comprehensive phase II and III trials, and investigation of elacestrant in combination with other drugs or in preoperative settings.
Retrospective data • Review • Journal
|
ER (Estrogen receptor)
|
HR positive
|
Orserdu (elacestrant)
25d
Initial real-world experience with ribociclib in advanced breast cancer. (PubMed, J Oncol Pharm Pract)
Although objective response rates were modest in this mixed cohort of heavily pretreated patients, ribociclib combined with letrozole or fulvestrant has shown robust PFS and OS in real-world practice. AEs related treatment discontinuation rate is higher than that reported in clinical trials with stringent inclusion criteria.
Journal • Real-world evidence
|
HER-2 (Human epidermal growth factor receptor 2)
|
HR positive • HER-2 negative • HR positive + HER-2 negative
|
Kisqali (ribociclib) • fulvestrant • letrozole
25d
ELEVATE: Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Patients With Metastatic Breast Cancer (clinicaltrials.gov)
P1/2, N=400, Recruiting, Stemline Therapeutics, Inc. | Trial completion date: Aug 2026 --> Dec 2028 | Trial primary completion date: Dec 2024 --> Dec 2026
Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDK4 (Cyclin-dependent kinase 4)
|
PIK3CA mutation
|
Ibrance (palbociclib) • everolimus • Piqray (alpelisib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • Truqap (capivasertib) • Orserdu (elacestrant)
25d
Enrollment open
|
Verzenio (abemaciclib) • giredestrant (GDC-9545)
27d
Oral SERDs: Transforming the treatment of advanced breast cancer-Insights from EMBER-3. (PubMed, Med)
The phase 3 EMBER-3 trial1 demonstrated that when compared to standard therapy, imlunestrant improved progression-free survival (PFS) in advanced ER+/HER2- breast cancer with ESR1 mutations. When combined with abemaciclib, it significantly improved PFS for the entire population. However, the absence of a biomarker-based control group limits broader conclusions, highlighting the need for trials incorporating specific standards in ER+/HER2- breast cancer.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
HER-2 negative • HER-2 mutation
|
Verzenio (abemaciclib) • Inluriyo (imlunestrant)
1m
Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • HER-2 negative
|
tamoxifen • Verzenio (abemaciclib) • giredestrant (GDC-9545)
1m
Optimizing therapeutic approaches for HR+/HER2- advanced breast cancer: clinical perspectives on biomarkers and treatment strategies post-CDK4/6 inhibitor progression. (PubMed, Cancer Drug Resist)
Actionable biomarkers, such as PIK3CA and ESR1 mutations, have emerged as pivotal tools to guide second-line treatment decisions, enabling the use of targeted therapies like alpelisib and elacestrant and emphasizing the important role of biomarkers in guiding the selection of therapy. This overview aims to provide clinicians with a practical and up-to-date framework to inform treatment decisions and improve patient care in the context of this challenging disease. Additionally, we review emerging biomarkers and novel treatment strategies to address this difficult clinical landscape.
Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
|
HR positive • HER-2 negative • PIK3CA mutation • EGFR negative
|
Piqray (alpelisib) • Orserdu (elacestrant)
1m
RET inhibition overcomes resistance to combined CDK4/6 inhibitor and endocrine therapy in ER+ breast cancer. (PubMed, Front Oncol)
The functional role of RET was assessed by siRNA-mediated RET silencing and targeted inhibition with the FDA/EMA-approved RET-selective inhibitor selpercatinib in resistant breast cancer cells and patient-derived organoids (PDOs)...We show that RET is upregulated in ER+ breast cancer cell lines resistant to combined CDK4/6i and fulvestrant compared to isogenic cells resistant to fulvestrant alone...We further observed a shorter median survival to combined CDK4/6i and endocrine therapy in patients with RET-positive compared to RET-negative tumors, but this difference did not reach statistical significance. Our findings show that RET is overexpressed in ER+ metastatic breast cancer resistant to combined CDK4/6i and endocrine therapy, rendering RET inhibition a promising therapeutic approach for patients who experience disease progression on combined CDK4/6i and endocrine therapy.
Journal
|
ER (Estrogen receptor) • RET (Ret Proto-Oncogene)
|
ER positive • RET positive
|
Retevmo (selpercatinib) • fulvestrant
1m
Exploration of telomere-related biomarkers for lung adenocarcinoma and targeted drug prediction. (PubMed, Discov Oncol)
This study provided novel diagnostic biomarkers, therapeutic targets, and potential drugs for LUAD.
Journal
|
TOP2A (DNA topoisomerase 2-alpha) • PLK1 (Polo Like Kinase 1) • CDC20 (Cell Division Cycle 20) • CCNB1 (Cyclin B1)
|
fulvestrant
1m
Trial completion
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
HER-2 negative
|
giredestrant (GDC-9545) • Soltamox (tamoxifen citrate)
1m
Sodium Danshensu Alleviates Bone Cancer Pain by Inhibiting the Osteoclast Differentiation and CGRP Expression. (PubMed, Eur J Pharmacol)
SDSS relieves bone cancer pain by inhibiting osteoclast activity, providing a potential new drug option for cancer pain patients.
Journal
|
CTSK (Cathepsin K) • NFATC1 (Nuclear Factor Of Activated T Cells 1) • FOS (Fos Proto-Oncogene AP-1 Transcription Factor Subunit 2)
|
fulvestrant
1m
Treatment sequences and survival outcomes in advanced HR + HER2- breast cancer patients: a real-world cohort. (PubMed, Breast Cancer Res Treat)
In this real-world cohort, we observed a wide variety of different treatment sequences applied in daily clinical practice, some of which were in discordance with the current guidelines. Fear that patients may never get around to treatment with CDK4/6i if a patient did not start with a CDK4/6i was not supported by our study results.
Journal • Real-world evidence
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 negative
|
tamoxifen • fulvestrant
2ms
Inavolisib: First Approval. (PubMed, Drugs)
On 10 October 2024, inavolisib received its first approval in the USA in combination with palbociclib and fulvestrant for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. In the EU and other countries worldwide, regulatory review of inavolisib is currently underway. This article summarises the milestones in the development of inavolisib leading to this first approval for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer.
Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
|
HR positive • HER-2 negative • PIK3CA mutation
|
Ibrance (palbociclib) • fulvestrant • Itovebi (inavolisib)
2ms
AMEERA-3: Phase 2 Study of Amcenestrant (SAR439859) Versus Physician's Choice in Locally Advanced or Metastatic ER-positive Breast Cancer (clinicaltrials.gov)
P2, N=367, Terminated, Sanofi | Active, not recruiting --> Terminated; Sponsor decision to prematurely stop the study, not linked to any safety concern.
Trial termination
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • HER-2 negative
|
tamoxifen • fulvestrant • letrozole • anastrozole • exemestane • amcenestrant (SAR439859)
2ms
New Oral Selective Estrogen Receptor Degraders Redefine Management of Estrogen Receptor-Positive Breast Cancer. (PubMed, Annu Rev Med)
There are currently five oral SERDs in published and ongoing clinical trials-elacestrant, camizestrant, giredestrant, imlunestrant, and amcenestrant-with more in development. They offer a reasonably well-tolerated oral therapy option with low discontinuation rates in studies. This review summarizes the currently available literature on this new class of drugs.
Review • Journal
|
ER (Estrogen receptor)
|
ER positive
|
Orserdu (elacestrant) • amcenestrant (SAR439859) • Inluriyo (imlunestrant) • camizestrant (AZD9833) • giredestrant (GDC-9545)
2ms
Evaluating the Effectiveness of Cyclin-Dependent Kinase 4/6 Inhibitors in Early- and Very Early-Onset Metastatic Breast Cancer: A Multicenter Study. (PubMed, Medicina (Kaunas))
This study aims to evaluate the efficacy of ribociclib and palbociclib with ET in HR+/HER2- metastatic breast cancer, addressing the critical gap in understanding treatment outcomes in younger patient populations...Additional factors associated with poorer outcomes included liver metastasis, progesterone receptor negativity, high tumor grade, and the concurrent use of fulvestrant with CDK4/6 inhibitors...The findings underscore the urgent need for personalized treatment strategies, routine genetic testing, and dedicated clinical trials designed to address the specific needs of these high-risk subgroups. By advancing our understanding of the clinical and molecular landscape of early-onset breast cancer and very early-onset breast cancer, this study lays the groundwork for improving outcomes in these underserved patients through tailored therapeutic approaches.
Clinical • Retrospective data • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor)
|
HR positive • HER-2 negative • HR positive + HER-2 negative
|
Ibrance (palbociclib) • Kisqali (ribociclib) • fulvestrant
2ms
Discovery of D-Ring-Contracted Artemisinin as a Potent Hydrophobic Tag for Targeted Protein Degradation. (PubMed, J Med Chem)
We have crafted a series of conjugates by fusing D-ring-contracted artemisinin with raloxifene, and among these, RA3 has emerged as a promising candidate for degrading estrogen receptor α (ERα). In a breast cancer xenograft mouse model, RA3 induced pronounced tumor growth inhibition, surpassing the performance of the FDA-approved ERα degrader, Faslodex. Furthermore, the versatility of D-ring-contracted artemisinin as a hydrophobic tag has been confirmed in its ability to enhance the degradation of cyclin-dependent kinase 6 (CDK6) and histone deacetylases (HDACs). Our work not only underscores the therapeutic potential of artemisinin derivatives in targeted protein degradation but also paves new avenues for advancing the field of protein-based drug design.
Journal
|
ER (Estrogen receptor) • CDK6 (Cyclin-dependent kinase 6)
|
fulvestrant • raloxifene hydrochloride
2ms
Endocrine-targeting therapies shift the breast microbiome to reduce estrogen receptor-α breast cancer risk. (PubMed, Cell Rep Med)
We demonstrate that endocrine-targeting therapies, such as tamoxifen, reshape the non-cancerous breast microbiome to influence tissue metabolism and reduce tumorigenesis...Human tumor samples revealed that LTA-positive bacteria negatively correlated with Ki67, suggesting that endocrine therapies influence tumor-associated microbiota to regulate proliferation. Our data indicate that endocrine-targeting therapies modify the breast microbiome, corresponding with a shift in tissue metabolism to potentially reduce ER+ breast cancer risk.
Journal
|
ER (Estrogen receptor)
|
ER positive
|
tamoxifen • fulvestrant
2ms
Cell-free tumor DNA analysis in advanced or metastatic breast cancer patients: mutation frequencies, testing intention, and clinical impact. (PubMed, Precis Clin Med)
The high prevalence of somatic alterations in TP53, PIK3CA, ESR1, and BRCA1/2 genes, identified by ctDNA genotyping, highlights their potential as biomarkers for targeted therapies. Detection of specific mutations affected treatment decisions, such as eligibility for alpelisib, and might further facilitate treatment with e.g. elacestrant or capiversatib in future treatment lines.
Journal • BRCA Biomarker
|
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) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
|
HR positive • HER-2 negative • PIK3CA mutation • EGFR positive
|
Guardant360® CDx
|
Piqray (alpelisib) • Orserdu (elacestrant)
2ms
Elacestrant in women with estrogen receptor-positive and HER2-negative early breast cancer: results from the preoperative window-of-opportunity ELIPSE trial. (PubMed, Clin Cancer Res)
Preoperative treatment with elacestrant in early BC demonstrated relevant biological and molecular responses and exhibited a manageable safety profile. These findings support further investigation of elacestrant in the early setting.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • GZMB (Granzyme B)
|
HER-2 positive • ER positive • HER-2 negative • ER positive + HER-2 negative • HER-2 negative + ER positive
|
Prosigna™ Breast Cancer Prognostic Gene Signature Assay
|
Orserdu (elacestrant)
2ms
Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden. (PubMed, NPJ Breast Cancer)
Building on previous research that identified metastatic-niche-specific metabolic vulnerabilities, we investigated how a ketogenic diet enhances estrogen receptor (ER)-positive liver metastatic breast cancer's response to Fulvestrant (Fulv) treatment...We also explored interactions between glucose, palmitic acid, and β-hydroxybutyric acid. These findings establish the molecular basis and clinical potential of a ketogenic diet to enhance Fulv efficacy in patients with ER+ liver metastatic breast cancer, potentially improving survival outcomes and quality of life in this population.
Journal
|
ER (Estrogen receptor) • OXCT1 (3-Oxoacid CoA-Transferase 1)
|
ER positive
|
fulvestrant
2ms
Predictive and prognostic value of 18F-FES PET/CT for patients with recurrent or metastatic breast cancer treated with endocrine therapy plus cyclin-dependent kinase 4/6 inhibitors. (PubMed, Eur J Nucl Med Mol Imaging)
ER expression determined by 18F-FES PET/CT predicted the efficacy of CDK4/6 inhibitor-based endocrine therapy and was prognostic for survival in recurrent/metastatic ER-positive, HER2-negative breast cancer.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • HER-2 negative • ER expression • HER-2 negative + ER positive
|
fulvestrant
2ms
ERα dysfunction caused by ESR1 mutations and therapeutic pressure promotes lineage plasticity in ER+ breast cancer. (PubMed, Nat Cancer)
ESR1-mutant tumors generally retained luminal features and higher ERα activity and exhibited an anti-proliferative response to the ERα antagonist giredestrant. ESR1-mutant tumors acquired mixed-lineage features following treatment. Lineage heterogeneity in advanced ER+ breast cancer may underpin the differential benefit of investigational ERα therapeutics observed in ESR1-mutant versus NMD contexts.
Journal
|
ER (Estrogen receptor)
|
ER mutation • ESR1 mutation
|
giredestrant (GDC-9545)
2ms
Evaluation of Orally Administered Amcenestrant (SAR439859) in Japanese Postmenopausal Patients With Advanced Breast Cancer (AMEERA-2) (clinicaltrials.gov)
P1, N=10, Terminated, Sanofi | Active, not recruiting --> Terminated; Sponsor decision to prematurely stop the study, not linked to any safety concern.
Trial termination
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
amcenestrant (SAR439859)
2ms
Transformer-based modeling of Clonal Selection and Expression Dynamics reveals resistance mechanisms in breast cancer. (PubMed, NPJ Syst Biol Appl)
When applied to cells treated with either giredestrant, a selective estrogen receptor (ER) antagonist and degrader, or palbociclib, a CDK4/6 inhibitor, pathways dynamically associated with resistance are revealed. Clustering based on partial least squares regression found that high baseline expression of both SNHG25 and SNCG genes was the primary marker of positive selection to co-treatment and thus potentially associated with innate resistance - an aspect that traditional differential analysis methods missed. In conclusion, TraCSED enables associating features with phenotypes in a time-dependent manner from scRNA-seq data.
Journal
|
ER (Estrogen receptor) • SNHG5 (Small Nucleolar RNA Host Gene 5)
|
Ibrance (palbociclib) • giredestrant (GDC-9545)
2ms
Oxidative Phosphorylation is a Metabolic Vulnerability of Endocrine Therapy-Tolerant Persister Cells in ER+ Breast Cancer. (PubMed, Cancer Res)
In an analysis of tumor specimens from 32 patients, tumors exhibiting residual cell proliferation after aromatase inhibitor-induced estrogen deprivation with letrozole showed increased mitochondrial content. Pharmacological inhibition of mitochondrial complex I suppressed the tumor-forming potential of persisters in mice and synergized with the anti-estrogen fulvestrant to induce regression of patient-derived xenografts. These findings indicate that mitochondrial metabolism is essential in endocrine-tolerant persister ER+ breast cancer cells and warrant the development of treatment strategies to leverage this vulnerability for treating breast cancer.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • HER-2 negative
|
fulvestrant • letrozole
2ms
Oral selective estrogen receptor degraders for breast cancer treatment: focus on pharmacological differences. (PubMed, Breast Cancer Res Treat)
Somatic activating mutations of the estrogen receptor 1 (ESR1) gene are known to sustain ER activity, boost ER-dependent gene transcription, and foster resistance to ET. The most significant gap remains after treatment failure with ET and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors, where fulvestrant monotherapy typically results in a median progression-free survival of 2-3 months. Novel compounds, including oral SERDs, have been explored for their potential to overcome therapeutic resistance, both as monotherapy and in combination with other targeted therapies. Herein, we provide an overview on the latest findings on oral SERDs, examining their mechanism of action, safety data, and pharmacokinetics and pharmacodynamics profiles.
Review • Journal
|
ER (Estrogen receptor)
|
HR positive
|
fulvestrant
2ms
Trial completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • HER-2 negative • HER-2 negative + ER positive
|
fulvestrant • anastrozole
2ms
EMPRESS: Preoperative Window Opportunity Study with Giredestrant or Tamoxifen in Premenopausal Women with ER+/HER2[-] & Ki67≥10% (clinicaltrials.gov)
P2, N=92, Active, not recruiting, MedSIR | Recruiting --> Active, not recruiting | Trial primary completion date: Nov 2024 --> Feb 2025
Enrollment closed • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
HER-2 negative
|
giredestrant (GDC-9545) • Soltamox (tamoxifen citrate)
2ms
Endocrine-targeting therapies shift the breast microbiome to reduce estrogen receptor-α breast cancer risk. (PubMed, Cell Rep Med)
We demonstrate that endocrine-targeting therapies, such as tamoxifen, reshape the non-cancerous breast microbiome to influence tissue metabolism and reduce tumorigenesis...Human tumor samples revealed that LTA-positive bacteria negatively correlated with Ki67, suggesting that endocrine therapies influence tumor-associated microbiota to regulate proliferation. Our data indicate that endocrine-targeting therapies modify the breast microbiome, corresponding with a shift in tissue metabolism to potentially reduce ER+ breast cancer risk.
Journal
|
ER (Estrogen receptor)
|
ER positive
|
tamoxifen • fulvestrant