AI Article Synopsis
Article Abstract
Background: Endocrine therapy is recommended as a first-line treatment for hormone receptor-positive metastatic breast cancer (HR+MBC) patients. No biomarker has been validated to predict tumor progression in that setting. We aimed to prospectively compare the risk of early progression according to circulating ESR1 mutations, CA-15.3, and circulating cell-free DNA in MBC patients treated with a first-line aromatase inhibitor (AI).
Methods: Patients with MBC treated with a first-line AI were prospectively included. Circulating biomarker assessment was performed every 3 months. The primary objective was to determine the risk of progression or death at the next follow-up visit (after 3 months) in case of circulating ESR1 mutation detection among patients treated with a first-line AI for HR+MBC.
Results: Overall, 103 patients were included, and 70 (68%) had progressive disease (PD). Circulating ESR1 mutations were detected in 22/70 patients with PD and in 0/33 patients without progression (p < 0.001). Among the ESR1-mutated patients, 18/22 had a detectable mutation prior to progression, with a median delay of 110 days from first detection to PD. The detection of circulating ESR1 mutations was associated with a 4.9-fold (95% CI 3.0-8.0) increase in the risk of PD at 3 months. Using a threshold value of 25% or 100%, a CA-15.3 increase was also correlated with progression (p < 0.001 and p = 0.003, respectively). In contrast to ESR1, the CA-15.3 increase occurred concomitantly with PD in most cases, in 27/47 (57%) with a 25% threshold and in 21/25 (84%) with a 100% threshold. Using a threshold value of either 25% or 100%, cfDNA increase was not correlated with progression.
Conclusion: The emergence of circulating ESR1 mutations is associated with a 4.9-fold increase in the risk of early PD during AI treatment in HR+MBC. Our results also highlighted that tracking circulating ESR1 mutations is more relevant than tracking CA-15.3 or cfDNA increase to predict progression in this setting.
Trial Registration: ClinicalTrials.gov, NCT02473120. Registered 16 June 2015-retrospectively registered after one inclusion (first inclusion 1 June 2015).
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254698 | PMC |
| http://dx.doi.org/10.1186/s13058-020-01290-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Molecular Profiling of Endocrine Resistance in HR+/HER2-Metastatic Breast Cancer: Insights from Extracellular Vesicles-Derived DNA and ctDNA in Liquid Biopsies.
Int J Mol Sci
December 2024
"Clinical and Translational Research in Oncology" Group, Molecular Oncology Laboratory, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), 28040 Madrid, Spain.
Standard treatments in hormone receptor-positive (HR+)/HER2-metastatic breast cancer (mBC) typically involve endocrine therapy (ET) combined with CDK4/6 inhibitors, yet resistance to ET remains a persistent challenge in advanced cases. A deeper knowledge of the use of liquid biopsy is crucial for the implementation of precision medicine in mBC with real-time treatment guidance. Our study assesses the prognostic value of and mutations in DNA derived from extracellular vesicles (EV-DNA) in longitudinal plasma from 59 HR+/HER2-mBC patients previously exposed to aromatase inhibitors, with a comparative analysis against circulating tumor DNA (ctDNA).
View Article and Find Full Text PDFCirculating Tumor DNA in Early and Metastatic Breast Cance-Current Role and What Is Coming Next.
Cancers (Basel)
November 2024
Department of Gynecology and Obstetrics, University Hospital Düsseldorf, 40225 Duesseldorf, Germany.
The progress that has been made in recent years in relation to liquid biopsies in general and circulating tumor DNA (ctDNA) in particular can be seen as groundbreaking for the future of breast cancer treatment, monitoring and early detection. Cell-free DNA (cfDNA) consists of circulating DNA fragments released by various cell types into the bloodstream. A portion of this cfDNA, known as ctDNA, originates from malignant cells and carries specific genetic mutations.
View Article and Find Full Text PDFGenomic landscape of circulating tumor DNA in HER2-low metastatic breast cancer.
Signal Transduct Target Ther
December 2024
Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Article Synopsis
- The study analyzed data from 1071 metastatic breast cancer patients to explore the characteristics and treatment impacts of those with HER2-low status, emphasizing the need for improved clinical guidance in this population.
- Key mutations found in HER2-low patients include TP53, PIK3CA, and ESR1, which are linked to metabolic changes and could influence treatment responses.
- Results indicate that while HER2-low and HER2-0 patients generally respond similarly to standard treatments, those with specific genetic mutations may benefit more from personalized approaches, supporting the development of tailored treatment strategies based on tumor characteristics.
Developmental expression patterns of gonadal hormone receptors in arcuate kisspeptin and GABA neurons of the postnatal female mouse.
J Neuroendocrinol
November 2024
Centre for Neuroendocrinology, Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
The arcuate nucleus of the hypothalamus (ARC) is central in the neuronal regulation of fertility and reproduction through translating gonadal steroid hormone cues into the GnRH signaling pathway in the brain. Evidence suggests that circulating gonadal steroids play an important role in modulating female reproduction via kisspeptin and γ-aminobutyric acid (GABA) neurons in the ARC in both development and adulthood. However, the temporal onset of these ARC neurons' sensitivity to gonadal steroids is unknown.
View Article and Find Full Text PDFTaoren Honghua Decoction alleviates atherosclerosis by inducing autophagy and inhibiting the PI3K-AKT signaling pathway to regulate cholesterol efflux and inflammatory responses.
Int Immunopharmacol
January 2025
Department of Cardiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address:
Background: Taoren Honghua Decoction (THD) is a traditional Chinese formula known for enhancing blood circulation and demonstrating clinical efficacy in the treatment of cardiovascular and cerebrovascular diseases. However, the primary active components and the underlying mechanisms by which THD exerts its therapeutic effects on atherosclerosis (AS) remain insufficiently characterized.
Objective: This study aims to systematically validate the protective effects of THD on AS and elucidate its potential molecular mechanisms through an integrative approach involving network pharmacology, in vivo, and in vitro experiments.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!