Highlighting Liquid Biopsy Advances at the 13th Congress of the Hungarian Society of Clinical Oncology
At the presentation, it was discussed that the current evaluation of treatment response in solid tumors mainly depends on imaging-based measurements of tumor size changes. However, functional changes in the tumor first occur at the regulatory level, at the DNA and RNA stages, meaning morphological changes are only detectable after significant tumor volume alteration. This limits the usefulness of radiological response criteria for early assessment of therapy effectiveness. In contrast, dynamic changes in circulating tumor DNA (ctDNA) can predict tumor response much earlier in the course of treatment, well before imaging methods detect changes. Multiple clinical studies have confirmed the applicability of ctDNA-based response criteria in advanced breast cancer, leading the National Comprehensive Cancer Network to accept liquid biopsy as a diagnostic sample source for identifying mutations such as PIK3CA, AKT, PTEN, and ESR1.
Tumors exhibit high genetic heterogeneity at diagnosis, and therapy exerts selective pressure that favors resistant subclones. Next-generation sequencing based on liquid biopsy is one of the best tools for regular tumor monitoring and discovering new molecular targets. ESR1 mutation serves as a marker of resistance to aromatase inhibitor therapy, which can be effectively targeted by the new SERD drug Elacestrant. Tracking dynamic changes of ESR1 mutant alleles in ctDNA helps optimize treatment strategies and improves survival outcomes. In our laboratory, we detected ESR1 mutations in over 30 cases before or during aromatase inhibitor treatment, and ctDNA monitoring predicted disease progression 2-6 months earlier than conventional imaging and biochemical methods. Overall, the clinical application of liquid biopsy has proven its value, identifying actionable pathogenic variants in 39% of cases. However, to draw accurate conclusions, it is essential to apply the appropriate test to the right patient.
