Current and Developing Liquid Biopsy Techniques for Breast Cancer

Abstract

Breast cancer is the most commonly diagnosed cancer and leading cause of cancer mortality among woman worldwide. The techniques of diagnosis, prognosis, and therapy monitoring of breast cancer are critical. Current diagnostic techniques are mammography and tissue biopsy; however, they have limitations. With the development of novel techniques, such as personalized medicine and genetic profiling, liquid biopsy is emerging as the less invasive tool for diagnosing and monitoring breast cancer. Liquid biopsy is performed by sampling biofluids and extracting tumor components, such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), cell-free mRNA (cfRNA) and microRNA (miRNA), proteins, and extracellular vehicles (EVs). In this review, we summarize and focus on the recent discoveries of tumor components and biomarkers applied in liquid biopsy and novel development of detection techniques, such as surface-enhanced Raman spectroscopy (SERS) and microfluidic devices.

Keywords: breast cancer; circulating tumor DNA; circulating tumor cells; extracellular vesicles; liquid biopsy; microRNA.

Figure 1

Comparison of liquid biopsy and tissue biopsy. Liquid biopsy is a minimally invasive method and relies on quantification of genetic materials derived from tumor cells and released into circulation, such as circulating tumor cells (CTCs), cell-free DNA (cfDNA)/circulating tumor DNA (ctDNA), circulating tumor RNA, extracellular vesicles (EVs), and circulating tumor proteins. Liquid biopsy allows for early diagnosis and screening, prediction of prognosis, early relapse detection in localized and locally advance breast cancer, minimal residual disease (MRD) identification, and longitudinal monitoring of the disease progression and treatment response. Therefore, liquid biopsy can be applied in as many time points as required during tumor progression and treatments, in order to detect recurrence and monitor response to treatment (green arrows). In contrast, tissue biopsy is an invasive procedure and not applicable for monitoring treatment response; subsequently, tissue biopsy is mainly applied at the time points for diagnosis and detection of recurrence during tumor progression (purple arrows).