The breast is yet to come: current and future utility of circulating tumour DNA in breast cancer

Abstract

Advances in genomic strategies and the development of targeted therapies have enabled precision medicine to revolutionise the field of oncology. Precision medicine uses patient-specific genetic and molecular information, traditionally obtained from tumour biopsy samples, to classify tumours and treat them accordingly. However, biopsy samples often fail to provide complete tumour profiling, and the technique is expensive and, of course, relatively invasive. Advances in genomic techniques have led to improvements in the isolation and detection of circulating tumour DNA (ctDNA), a component of a peripheral blood draw/liquid biopsy. Liquid biopsy offers a minimally invasive method to gather genetic information that is representative of a global snapshot of both primary and metastatic sites and can thereby provide invaluable information for potential targeted therapies and methods for tumour surveillance. However, a lack of prospective clinical trials showing direct patient benefit has limited the implementation of liquid biopsies in standard clinical applications. Here, we review the potential of ctDNA obtained by liquid biopsy to revolutionise personalised medicine and discuss current applications of ctDNA both at the benchtop and bedside.

Fig. 1. Schematic of sample processing for isolation of cfDNA.

Blood samples are collected in tubes made specifically to stabilize all cfDNA. The collected sample is then centrifuged and cfDNA-containing plasma is isolated. Remaining cellular contamination is eliminated with a final centrifugation, and cfDNA is isolated and purified through a variety of commercial kits.

Fig. 2. cfDNA technologies mentioned in this review.

Cell-free DNA is primarily analyzed for ctDNA content by PCR-based techniques or NGS-based techniques. In the PCR-based techniques few variants are probed at once whereas in NGS-based techniques many genes are queried in one sequencing run. Each technique has benefits and drawbacks regarding time, money, breadth, sensitivity, and scalability. Images were adapted from literature cited in the text.