Recent advances in deep amplicon sequencing have enabled rapid assessment of somatic mutations and structural changes in multiple cancer genes in DNA isolated from tumour tissues and circulating cell-free DNA (cfDNA). This cfDNA is under investigation as a “liquid biopsy” for the real time monitoring of patients with cancer in a growing number of research studies and clinical trials. Areas covered: Here we will provide a brief overview of the potential clinical utility of cfDNA profiling for detection and monitoring of patients with breast cancer. The review was conducted in English using PubMed and search terms including “breast cancer”, “plasma DNA”, “circulating cell free DNA” and “circulating tumour DNA”. Expert commentary: Liquid biopsies through circulating tumor DNA (ctDNA) enable monitoring of patients with breast cancer. The challenge ahead will be to incorporate cfDNA mutation profiling into routine clinical practice to provide patients with the most appropriate and timely treatment.