Circulating tumor biomarkers in early-stage breast cancer: characteristics, detection, and clinical developments

Breast cancer is the most common form of cancer in women, contributing to high rates of morbidity and mortality owing to the ability of these tumors to metastasize via the vascular system even in the early stages of progression. While ultrasonography and mammography have enabled the more reliable detection of early-stage breast cancer, these approaches entail high rates of false positive and false negative results Mammograms also expose patients to radiation, raising clinical concerns. As such, there is substantial interest in the development of more accurate and efficacious approaches to diagnosing breast cancer in its early stages when patients are more likely to benefit from curative treatment efforts. Blood-based biomarkers derived from the tumor microenvironment (TME) have frequently been studied as candidate targets that can enable tumor detection when used for patient screening. Through these efforts, many promising biomarkers including tumor antigens, circulating tumor cell clusters, microRNAs, extracellular vesicles, circulating tumor DNA, metabolites, and lipids have emerged as targets that may enable the detection of breast tumors at various stages of progression. This review provides a systematic overview of the TME characteristics of early breast cancer, together with details on current approaches to detecting blood-based biomarkers in affected patients. The limitations, challenges, and prospects associated with different experimental and clinical platforms employed in this context are also discussed at length.