Evaluation of ctDNA-based ESR1 testing in breast cancer: results from the first external quality assessment scheme in China.

Background: Circulating tumor DNA (ctDNA) testing of plasma for ESR1 somatic variants is essential for guiding treatment decisions in hormone receptor-positive (HR  +  ) and HER2-negative (HER2-) advanced or metastatic breast cancer (MBC) patients who have progressed on frontline therapy. To ensure optimal, uniform, and reliable ESR1 testing across China, an pilot external quality assessment (EQA) scheme was established.

Methods: Aliquots of five artificial reference plasma samples containing ESR1 mutations at varying allelic frequencies were distributed to 37 laboratories for testing and reporting according to routine procedures. The genotyping accuracy and clinical reporting were evaluated against standardized criteria, and feedback was provided to the participants.

Results: The overall genotyping error rate in the EQA was 6.29%, with 91.4% of laboratories correctly identifying the ESR1 mutational status in all samples. A variety of extraction methods and analytical techniques were employed. However, reports often failed to address the risk that tumor DNA may not have been tested, and the limitations of the methodologies used by participants were insufficiently discussed.

Conclusion: The variability in genotyping accuracy and reporting standards underscores the importance of EQA and educational guidance to ensure the provision of high-quality clinical services.