ArticleBMC cancer2025
Concurrent genomic assessment of circulating tumour cells and ctDNA to guide therapy in metastatic breast cancer.
Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMolecular analysis of actionable driver mutations and somatic copy number alterations (sCNAs) in circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) is increasingly being used to guide personalised medicine in patients with cancer. In previous CTC studies, high numbers of CTCs were needed for successful recovery of individual CTCs for molecular analysis at a time when patients typically have very short survival, limiting clinical applicability. Here, by performing longitudinal analyses of ctDNA and CTCs across a broad range of CTC counts, we hypothesized that CTCs could reveal synergistic and additional genomic information to ctDNA at points when therapeutic interventions could be considered in the follow up of patients with metastatic breast cancer (MBC).
methodsEight patients underwent serial blood sampling. CTCs were captured via CellSearch-DEPArray from 7.5 mL (CellSave tubes), while 15 mL (EDTA tubes) was used for cfDNA extraction. A total of 58 cfDNA samples and 192 CTCs from the 8 patients were compared by shallow whole genome sequencing sWGS and targeted next generation sequencing using custom designed mutation panels (cfDNA; dual barcoding Ion AmpliSeq HD technology (556 hotspots across 24 genes) and CTCs; SingleSeq-compatible AmpliSeq technology across 539 of the 556 (97%) hotspots).
resultsThe majority of patient samples showed complementary genomic information in CTCs and ctDNA from the same blood sample. However, genome changes were detected in CTCs from some blood samples that were ctDNA negative despite progression providing actionable information at times when ctDNA analysis was not informative. Across the CTCs and ctDNA, common regions of loss included chromosome 13q14 containing the RB1 gene, detected in 3 of 4 patients receiving CDK4/6 inhibitors and amplification of 17q12 containing the ERBB2 gene in 2 of the 7 patients with HER2 negative metastatic disease, suggesting evolution to HER2 positive disease.
conclusionsOur study shows that CTCs provide key information that would have been missed by ctDNA monitoring alone and extends CTC and cfDNA genomic profiling to patients with a broad range of CTC counts for blood-based monitoring of HER2 status and other clinically actionable targets for informing treatment decisions in metastatic disease.
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