Cell-free circulating tumor DNA analysis for breast cancer and its clinical utilization as a biomarker

Abstract

Circulating tumor DNA (ctDNA) in the blood of cancer patients contains much information on genetic and epigenetic profiles associated with cancer development, progression, and response to therapy. Analysis of ctDNA provides an opportunity for non-invasive sampling of tumor DNA repetitiously and therefore advance precision medicine. Recent development in massively parallel sequencing and digital genomic techniques support the analytical and clinical validity of ctDNA as a promising 'liquid biopsy' in human cancer. In this review, we discussed the current status of cell-free ctDNA including ctDNA biology, recently developed techniques for ctDNA detection, breast cancer specific detecting strategies, with a focus on clinical applications of ctDNA-based biomarkers in breast oncology.

Keywords: biomarker; breast cancer; ctDNA; liquid biopsy.

Figure 1. Tumor cells release small fragments of cell-free DNA into circulation by multiple mechanisms, including necroptosis, apoptosis, secretion from tumor cells, and so on

Several strategies can be used for the analysis of circulating tumor DNA, such as quantification of cfDNA, detection of cell-free DNA integrity, microsatellite alterations, gene mutations, methylation patterns, and nucleosome. Some potential clinical applications of ctDNA as liquid biopsy to breast cancer management include screening for cancer (potentially as a supplement to mammography), monitoring disease burden, predicting recurrence, determining prognosis, assessing therapy response, tracking clone evolution, and deciphering tumor heterogeneity.