Clinical Applications of Circulating Tumor DNA in Monitoring Breast Cancer Drug Resistance

Abstract

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide. Unfortunately, treatments often fail because of the development of drug resistance, the underlying mechanisms of which remain unclear. Circulating tumor DNA (ctDNA) is free DNA released into the blood by necrosis, apoptosis or direct secretion by tumor cells. In contrast to repeated, highly invasive tumor biopsies, ctDNA reflects all molecular alterations of tumors dynamically and captures both spatial and temporal tumor heterogeneity. Highly sensitive technologies, including personalized digital PCR and deep sequencing, make it possible to monitor response to therapies, predict drug resistance and tailor treatment regimens by identifying the genomic alteration profile of ctDNA, thereby achieving precision medicine. This review focuses on the current status of ctDNA biology, the technologies used to detect ctDNA and the potential clinical applications of identifying drug resistance mechanisms by detecting tumor-specific genomic alterations in breast cancer.

Keywords::

• blood
• breast cancer
• circulating tumor DNA
• drug resistance
• mutation

Author contributions

Y Liu retrieved the relevant literature and drafted the manuscript. Q Du and D Sun designed the structure of the article. R Han and M Teng critically revised the manuscript. S Chen and H You reviewed the final manuscript prior to submission. All authors read and approved the final manuscript.

Financial & competing interests disclosure

The work is supported by the National Natural Science Foundation of China (grant nos. 81473177 and 81502616), Shaanxi Province Key Research and Development Program (grant no. 2017SF-089) and Innovative Experiment for Postgraduates in Medicine project at Xi’an Jiaotong University (grant no. YJSCX-2018-12). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The work is supported by the National Natural Science Foundation of China (grant nos. 81473177 and 81502616), Shaanxi Province Key Research and Development Program (grant no. 2017SF-089) and Innovative Experiment for Postgraduates in Medicine project at Xi’an Jiaotong University (grant no. YJSCX-2018-12). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.