DNA methylation and breast cancer: A way forward (Review).

The current management of breast cancer (BC) lacks specific non‑invasive biomarkers able to provide an early diagnosis of the disease. Epigenetic‑sensitive signatures are influenced by environmental exposures and are mediated by direct molecular mechanisms, mainly guided by DNA methylation, which regulate the interplay between genetic and non‑genetic risk factors during cancerogenesis. The inactivation of tumor suppressor genes due to promoter hypermethylation is an early event in carcinogenesis. Of note, targeted tumor suppressor genes are frequently hypermethylated in patient‑derived BC tissues and peripheral blood biospecimens. In addition, epigenetic alterations in triple‑negative BC, as the most aggressive subtype, have been identified. Thus, detecting both targeted and genome‑wide DNA methylation changes through liquid‑based assays appears to be a useful clinical strategy for early detection, more accurate risk stratification and a personalized prediction of therapeutic response in patients with BC. Of note, the DNA methylation profile may be mapped by isolating the circulating tumor DNA from the plasma as a more accessible biospecimen. Furthermore, the sensitivity to treatment with chemotherapy, hormones and immunotherapy may be altered by gene‑specific DNA methylation, suggesting novel potential drug targets. Recently, the use of epigenetic drugs administered alone and/or with anticancer therapies has led to remarkable results, particularly in patients with BC resistant to anticancer treatment. The aim of the present review was to provide an update on DNA methylation changes that are potentially involved in BC development and their putative clinical utility in the fields of diagnosis, prognosis and therapy.