Role of ctDNA in Breast Cancer

Abstract

Breast cancer is currently classified by immunohistochemistry. However, technological advances in the detection of circulating tumor DNA (ctDNA) have made new options available for diagnosis, classification, biological knowledge, and treatment selection. Breast cancer is a heterogeneous disease and ctDNA can accurately reflect this heterogeneity, allowing us to detect, monitor, and understand the evolution of the disease. Breast cancer patients have higher levels of circulating DNA than healthy subjects, and ctDNA can be used for different objectives at different timepoints of the disease, ranging from screening and early detection to monitoring for resistance mutations in advanced disease. In early breast cancer, ctDNA clearance has been associated with higher rates of complete pathological response after neoadjuvant treatment and with fewer recurrences after radical treatments. In metastatic disease, ctDNA can help select the optimal sequencing of treatments. In the future, thanks to new bioinformatics tools, the use of ctDNA in breast cancer will become more frequent, enhancing our knowledge of the biology of tumors. Moreover, deep learning algorithms may also be able to predict breast cancer evolution or treatment sensitivity. In the coming years, continued research and the improvement of liquid biopsy techniques will be key to the implementation of ctDNA analysis in routine clinical practice.

Keywords: breast cancer; cancer diagnosis; ctDNA; liquid biopsy; personalized medicine.

Figure 1

(a) Early breast cancer and relation between breast cancer cells and the vascular system. (b) Main components found in blood samples, from left to right: lymphocyte cell, cfDNA, erythrocyte, ctDNA, platelet, CTC, exosome with ctDNA.