Molecular testing plays an increasingly important role in guiding treatment decisions for patients with metastatic breast cancer, particularly when resistance to endocrine therapy develops. Mutations in the ESR1 gene can contribute to reduced sensitivity to certain endocrine treatments, making their detection clinically relevant. A study examining the diagnostic utility of liquid biopsy explored how circulating cell-free DNA (cfDNA) testing can identify ESR1 mutations and other genomic alterations in routine clinical practice.
Researchers at Hannover Medical School in Germany analyzed liquid biopsy samples from 162 patients with metastatic breast cancer collected between January 2023 and June 2024. Using a laboratory-developed next-generation sequencing assay, investigators examined four genes with potential clinical significance: ESR1, PIK3CA, ERBB2, and TP53. The study also included matched metastatic tissue samples from 25 patients, allowing researchers to compare mutation detection between blood-based and tissue-based testing approaches.
Genomic alterations were identified in 88 patients, representing 54.3% of the study population. ESR1 mutations were detected in 42 patients (25.9%), while PIK3CA mutations were identified in 34.6%. Approximately 18.5% of patients had alterations involving two or three of the genes analyzed. Multiple ESR1 mutations were also identified in some samples, illustrating the molecular diversity that can develop during metastatic disease progression. These findings demonstrate the potential of liquid biopsy to capture clinically relevant genomic information without requiring an invasive tissue procedure.
Comparisons between liquid biopsy and metastatic tissue samples revealed important differences in mutation detection. Among the 25 patients with paired samples, some ESR1 mutations were detected exclusively in circulating DNA, while others were identified only in metastatic tissue. These discrepancies suggest that each testing method may capture different aspects of tumor biology. Investigators noted that liquid biopsy can be particularly useful when multiple metastatic sites are present, although a negative blood-based result may warrant additional tissue testing when clinically appropriate.
Overall, the study supports the feasibility of incorporating liquid biopsy into routine molecular testing for metastatic breast cancer. By identifying ESR1 mutations and other clinically relevant alterations, blood-based testing may help clinicians better understand mechanisms of endocrine resistance and evaluate potential treatment strategies. The researchers emphasized the importance of appropriate sample handling, reliable testing methods, and consideration of tissue-based analysis when liquid biopsy results are negative or inconclusive.
Source: Sandbothe M, et al. Diagnostic Utility of ESR1 Mutation Detection in Liquid Biopsy of Metastatic Breast Cancer Patients. PubMed | Full Text