M Murtaza, S-J Dawson, K Pogrebniak, OM Rueda, E Provenzano, J Grant, S-F Chin, DWY Tsui, F Marass, D Gale, HR Ali, P Shah, T Contente-Cuomo, H Farahani, K Shumansky, Z Kingsbury, S Humphray, D Bentley, SP Shah, M Wallis, N Rosenfeld, C Caldas
Circulating tumour DNA analysis can be used to track tumour burden and analyse cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here we follow a patient with metastatic ER-positive and HER2-positive breast cancer receiving two lines of targeted therapy over 3 years. We characterize genomic architecture and infer clonal evolution in eight tumour biopsies and nine plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing. Mutation levels in the plasma samples reflect the clonal hierarchy inferred from sequencing of tumour biopsies. Serial changes in circulating levels of sub-clonal private mutations correlate with different treatment responses between metastatic sites. This comparison of biopsy and plasma samples in a single patient with metastatic breast cancer shows that circulating tumour DNA can allow real-time sampling of multifocal clonal evolution.