WP8 is dedicated to developing and validating methods for detecting circulating tumour DNA (ctDNA) in patients with metastatic breast cancer, using samples from the MONITOR-RCT study. ctDNA consists of tumour-derived fragments in the bloodstream and offers a powerful way to gain real-time insights into disease burden and treatment response. However, detecting ctDNA is technically challenging due to its low abundance, making continuous method optimization essential.
To address this, WP8 compares tumour-guided and tumour-agnostic Whole Genome Sequencing (WGS) approaches. The tumour-guided strategy uses sequencing of tumour tissue to define patient-specific mutation profiles, which are then tracked in plasma using advanced algorithms and tools like INVAR2. When tumour tissue is unavailable, the tumour-agnostic approach infers ctDNA directly from plasma sequencing data through genome-wide copy number profiling, using software such as IchorCNA.
Preliminary findings show that both approaches have strong potential for early and sensitive detection of tumour progression, aligning closely with FDG-PET results and outperforming conventional CT in early response assessment. These workflows will form the basis for further validation within PREMIO COLLAB, ensuring that liquid biopsy becomes a reliable and flexible tool for precision monitoring in clinical practice.