Comprehensive Liquid Biopsy Testing in Metastatic Hormone Receptor-Positive HER2-Negative Breast Cancer Patients:
Karsten M Warwas1,2, Anna-Lena Volckmar3, Daniel Kazdal3
1Department of Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany.
Breast Care (Basel, Switzerland)
|July 25, 2026
Summary
Liquid biopsy (LBx) effectively identifies ESR1 mutations in metastatic breast cancer, guiding targeted endocrine therapy like elacestrant. This minimally invasive test is rapid and feasible for routine clinical use.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Liquid biopsy (LBx) offers minimally invasive molecular profiling of circulating tumor DNA.
- Early detection of actionable mutations in HR-positive, HER2-negative metastatic breast cancer is crucial for therapy selection.
- ESR1 mutations confer resistance to aromatase inhibitors and predict response to selective estrogen receptor degraders, yet real-world LBx data are limited.
Purpose of the Study:
- To evaluate the real-world feasibility and clinical utility of liquid biopsy for detecting ESR1 mutations in HR-positive, HER2-negative metastatic breast cancer.
- To assess the impact of LBx-guided molecular profiling on treatment decisions, particularly the use of elacestrant.
- To determine the turnaround time and repeatability of LBx in routine clinical practice.
Main Methods:
- Retrospective analysis of 162 patients with HR-positive, HER2-negative metastatic breast cancer undergoing LBx.
- Hybrid capture-based next-generation sequencing (NGS) with high read depth (∼5,000-7,000×) for multigene panel mutation profiling.
- Focus on the detection of ESR1 mutations and their therapeutic implications.
Main Results:
- ESR1 mutations were detected in 46 (28.4%) of 162 patients.
- Twenty patients (43.5%) received elacestrant based on LBx findings.
- LBx was feasible, rapid (∼8.7 days), and repeatable, directly influencing treatment decisions for timely targeted endocrine therapy.
Conclusions:
- Real-world data support the clinical utility of LBx in the metastatic setting for guiding endocrine therapy.
- LBx is a rapid, minimally invasive, and informative tool for identifying resistance mutations like ESR1 and directing treatment with agents such as elacestrant.
- Early integration of LBx into treatment algorithms is recommended, with consideration for repeat testing at disease progression.
