Circulating tumour DNA testing in metastatic breast cancer: Integration with tissue testing

Breast cancer biomarker profiling predominantly relies on tissue testing (surgical and/or biopsy samples). However, the field of liquid biopsy, particularly the analysis of circulating tumour DNA (ctDNA), has witnessed remarkable progress and continues to evolve rapidly. The incorporation of ctDNA-based testing into clinical practice is creating new opportunities for patients with metastatic breast cancer (MBC). ctDNA offers advantages over conventional tissue analyses, as it reflects tumour heterogeneity and enables multiple serial biopsies in a minimally invasive manner. Thus, it serves as a valuable complement to standard tumour tissues and, in certain instances, may even present a potential alternative approach. In the context of MBC, ctDNA testing proves highly informative in the detection of disease progression, monitoring treatment response, assessing actionable biomarkers, and identifying mechanisms of resistance. Nevertheless, ctDNA does exhibit inherent limitations, including its generally low abundance, necessitating timely blood samplings and rigorous management of the pre-analytical phase. The development of highly sensitive assays and robust bioinformatic tools has paved the way for reliable ctDNA analyses. The time has now come to establish how ctDNA and tissue analyses can be effectively integrated into the diagnostic workflow of MBC to provide patients with the most comprehensive and accurate profiling. In this manuscript, we comprehensively analyse the current methodologies employed in ctDNA analysis and explore the potential benefits arising from the integration of tissue and ctDNA testing for patients diagnosed with MBC. This review article critically evaluates the rational for the application of circulating tumour DNA (ctDNA) testing in metastatic breast cancer and presents the currently available methods for ctDNA analyses. By discussing the intrinsic limitations of tissue and liquid biopsy, the importance of combinatory approaches to provide patients with the most comprehensive and accurate profiling are highlighted.This review scrutinizes the use of circulating tumour DNA testing in metastatic breast cancer and details the available testing methods. It emphasises the necessity of combined strategies for thorough and precise profiling, considering the inherent limitations of tissue and liquid biopsies.image