Analysis of circulating tumor DNA in breast cancer as a diagnostic and prognostic biomarker

Abstract

Despite all the advances in diagnosis and treatment of breast cancer, a large number of patients suffer from late diagnosis or recurrence of their disease. Current available imaging modalities do not reveal micrometastasis and tumor biopsy is an invasive method to detect early stage or recurrent cancer, signifying the need for an inexpensive, non-invasive diagnostic modality. Cell-free tumor DNA (ctDNA) has been tried for early detection and targeted therapy of breast cancer, but its diagnostic and prognostic utility is still under investigation. This review summarizes the existing evidence on the use of ctDNA specifically in breast cancer, including detection methods, diagnostic accuracy, role in genetics and epigenetics evaluation of the tumor, and comparison with other biomarkers. Current evidence suggests that increasing levels of ctDNA in breast cancer can be of significant diagnostic value for early detection of breast cancer although the sensitivity and specificity of the methods is still suboptimal. Additionally, ctDNA allows for characterizing the tumor in a non-invasive way and monitor the response to therapy, although discordance of ctDNA results with direct biopsy (i.e. due to tumor heterogeneity) is still considered a notable limitation.

Clinical Relevance of Liquid Biopsy in Melanoma and Merkel Cell Carcinoma

“…Indeed, due to it short half-life (about 2 h), it is representative of the real-time molecular changes in the tumor [53] and might alert about the emergence of new mutations. CtDNA has been used as a biomarker in patients with breast [54,55], colon [56] and lung [57,58] cancer, and its presence has been linked to the diagnosis [59,60], prognosis [61][62][63] and also follow-up of the disease [50,[64][65][66][67][68]. CtDNA level has been associated with the overall response rate and also with PFS [47,69].…”

The Labyrinth of Product Development and Regulatory Approvals in Liquid Biopsy Diagnostics

“…Performance requirements for liquid biopsies represent a major analytical challenge for NGS chemistries and hardware. As companion diagnostics, liquid biopsies require somatic variant detection in <30 ng total DNA and tumor fractions < 0.1% …”

“…As companion diagnostics, liquid biopsies require somatic variant detection in <30 ng total DNA and tumor fractions < 0.1%. 68 Sequencing chemistries developed for liquid biopsies can reach nominal specifications in this range for singlenucleotide variations but may fail to reach them for other variant types. 69 These analytical challenges are superimposed on a biological and clinical variability, which make consistent diagnostic detection of specific variants in oncology patients a difficult goal.…”

The Innovations, Advances and Outlooks of Liquid Biopsy in Oncology: A Literature Review

“…Advances in the understanding of molecular biology of cancer have led to the development of the Liquid Biopsy, which is a revolutionary new and reproducible technique, serving for the early detection of malignant neoplasms, as well as for the initiation of personalized and precise treatment, analysis of treatment response in real time, in addition to the prognosis of patients. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] This tool is currently called the Net Biopsy and uses the detection of biomarkers of cancer cells, such as circulating tumor cells (CTCs), circulating cell DNA (cfDNA), DNA of tumor cells (ctDNA) and exosomes, which can be detected in various fluids, such as blood, plasma and serum, urine, saliva and cerebrospinal fluid (CSF) . [2][3][4][5][6][7][8][9][10][11] This new diagnostic technique can be performed non-invasively or minimally invasive and may offer many advantages over conventional tissue biopsies.…”

“…[2][3][4][5][6][7][8][9][10][11] This new diagnostic technique can be performed non-invasively or minimally invasive and may offer many advantages over conventional tissue biopsies. [1][2][3][4]6,7,[10][11][12][13][14][15][16][17][18][19][20] This new technology can develop a new concept of individualized or personalized therapy, favoring an understanding that the same type of cancer and in the same stage of disease may have different treatments in different patients, because the liquid biopsy may also verify the heterogeneity and some types of tumor mutations and resistance to some types of drugs used in chemotherapy. 2,4,5,8,9,17 This approach, however, requires the development of reliable biomarkers and biosensors.…”