Abstract
Examination of tumor molecular characteristics by liquid biopsy is likely to greatly influence personalized cancer patient management. Analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and tumor-derived exosomes, all collectively referred to as “liquid biopsies,” are not only a modality to monitor treatment efficacy, disease progression, and emerging therapy resistance mechanisms, but they also assess tumor heterogeneity and evolution in real time. We review the literature concerning the examination of ctDNA and CTC in a diagnostic setting, evaluating their prognostic, predictive, and monitoring capabilities. We discuss the advantages and limitations of various leading ctDNA/CTC analysis technologies. Finally, guided by the results of clinical trials, we discuss the readiness of cell-free DNA and CTC as routine biomarkers in the context of various common types of neoplastic disease. At this moment, one cannot conclude whether or not liquid biopsy will become a mainstay in oncology practice.
Highlights
Testing of bodily fluids in medical diagnostics has a long history with Greek humorism and the Indian Ayurveda system as prominent examples
Many cells and tissues release some of their constituents to the bloodstream, including fragmented, cellfree DNA which can arise from tumor cells, i.e., circulating tumor DNA
The same cellfree DNA (cfDNA) mutations were found in 22% of 110 stage I–III BC patients [64], indicating a prognostic value for circulating tumor DNA (ctDNA) AFs: higher values correlated with shorter recurrence-free survival (RFS) and overall survival (OS) [64] which holds true for TNBC, too [65]. ctDNA detection in stage II–III TNBC patients with residual disease after neoadjuvant chemotherapy predicts recurrence with high specificity, but moderate sensitivity [66], potentially due to low plasma volume (1 ml) and a non-optimized NGS approach. ctDNA content shows significant correlation with prognosis at early cancer stages, as opposed to conventional protein tumor markers [64]
Summary
Testing of bodily fluids in medical diagnostics has a long history with Greek humorism and the Indian Ayurveda system as prominent examples. CtDNA detection in stage II–III TNBC patients with residual disease after neoadjuvant chemotherapy predicts recurrence with high specificity, but moderate sensitivity [66], potentially due to low plasma volume (1 ml) and a non-optimized NGS approach. Stage Finding eBC Circulating tumor DNA (ctDNA) can be detected in eBC before and after surgery I–III ctDNA mutation level as prognostic factor for recurrence-free survival (RFS) and overall survival (OS) eBC Presence of PIK3CA mutations in cell-free DNA (cfDNA) prognostic of RFS and breast cancer-specific survival (BCSS) in TNBC II–III Presence of ctDNA in TNBC patients with residual disease correlates with inferior disease-free survival (DFS) eBC Postoperative ctDNA mutation level predictive of early recurrence n.s. Aberrant methylation of six genes (SFN, P16, hMLH1, HOXD13, PCDHGB7, and RASSF1a) in serum cfDNA of breast cancer patients in comparison to the healthy subjects and those with benign breast disease. Presence of CTCs before and after chemotherapy associated with poorer DFS (p < 0.0001), breastcancer-specific survival (p < 0.008), and OS (p < 0.0002)
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