Predicting treatment resistance and relapse through circulating DNA

Abstract

The use of circulating DNA(ctDNA) to provide a non-invasive, personalised genomic snapshot of a patients' tumour has huge potential. Over the past five years this area of research has gained huge momentum. A number of studies in metastatic breast cancer have shown the potential of ctDNA to predict prognosis and treatment response using ctDNA. Further developments have included deeper sequencing using whole exome and shallow whole genome approaches which has the potential to identify new mutations and chromosomal copy number changes which appear upon resistance to treatment. In early breast cancer, recent work utilising personalised digital PCR probes has shown huge potential in predicting disease relapse and the detection of micrometastatic disease which could lead to improved treatment and outcome for these patients. Specific pathways of resistance can also be monitored and liquid biopsy approaches for the detection of ESR1 mutations have been used which could identify patients who have become resistant to particular endocrine therapies. The identification of PIK3CA mutations in plasma has also been shown to predict a higher response rate to specific PI3K inhibitors and could be used as a non-invasive screening tool prior to treatment. Further work on the detection of exosomal miRNA and hypermethylated DNA in plasma have shown promise in terms of specificity for early breast cancer detection and could be used to monitor treatment response. This review will focus on technological advances in the field, early detection of relapse and the detection of tumour-specific genomic alterations which could predict treatment response and resistance in patients with breast cancer.