Current breast cancer (BC) diagnostics include detailed pathological and genetic analysis for biological subtype identification; however, throughout the course of the disease, new alterations determining the progression of the disease or resistance to treatment appear. The tests based on liquid biopsy allow minimally invasive real-time monitoring of tumour-specific alteration during the entire disease treatment. Tumour-specific genetic material fragments occur in bodily fluids, and cell-free nucleic acids are a convenient tool for analysing genetic and epigenetic changes in tumours. Evidence for the diagnostic and prognostic value of epigenetic biomarkers is gradually increasing. Although, up to date, there is limited access to in vitro diagnostic (IVD) epigenetic liquid biopsy-based tests for BC management, the data on the clinical potential of such tests and biomarkers are accumulating rapidly.

In this review, we focused on research involving cell-free DNA methylation biomarkers in blood serum or plasma samples from BC patients.

Our review systematises data from genome-wide and targeted studies of DNA methylation changes in liquid biopsies from BC patients, aiming to highlight the most critical biomarkers suitable for early BC diagnosis, treatment personalisation and prognosis.

In summary, cell-free DNA methylation biomarkers show strong potential to enhance breast cancer diagnosis, prognosis, and personalised treatment through integrated clinical profiling.