Clinical utility of liquid biopsy in breast cancer: A systematic review

Abstract

Advancements in genetic sequencing techniques along with the identification of specific mutations and structural changes in multiple cancer genes, make it possible to identify circulating tumor cells and cell free nucleic acids as blood-based biomarkers, serving as a liquid biopsy (LB) with great utility for the diagnosis, treatment and follow-up of patients with neoplasms. This systematic review focuses on the clinical utility of LB in patients with breast cancer (BC). Articles published between 1990 and 2021 were included. Databases searched: Trip Database, WoS, EMBASE, PubMed, SCOPUS, and Clinical Keys. Variables studied: Publication year, country, number of cases, primary study design, LB detection methods, genes found, overall survival, disease-free survival, stage, response to treatment, clinical utility, BC molecular type, systemic treatment and methodological quality of primary studies. Of 2619 articles, 74 were retained representing 12 658 patients, mainly cohort studies (66.2%), the majority were from China (15%) and Japan (12.2%). All primary studies described clinical stage and type of systemic treatment used. Most used biomarker detection method: DNA (52.7%) and type of analysis: quantification of total cfDNA (35.1%).PIK3CA mutation was most frequent (62.9%). Evidence suggests clinically useful applications of BC. Though heterogeneous, publications suggest that LB will constitute part of the standard diagnostic-therapeutic process of BC.

Size and Methylation Index of Cell-Free and Cell-Surface-Bound DNA in Blood of Breast Cancer Patients in the Contest of Liquid Biopsy

“…Currently, circulating tumor cells, cfDNA, small RNAs, and exosomes are used for liquid biopsy [ 31 , 32 , 33 ]. The advantages of circulating genetic markers include the opportunity to detect neoplasia-associated point mutations, deletions/inserts, translocations, and amplifications, as well as aberrant cytosine methylation in the CpG-dinucleotides of tumor suppressor genes [ 1 ]. To date, aberrant DNA methylation has been shown to be one of the most common and early causes of malignant cell transformation and tumors of different localizations, including breast cancer.…”

“…Cancer-specific DNA with genetic and epigenetic alterations identical to tumor DNA usually circulates in the blood of patients with oncological diseases [ 1 ]. Epigenetic DNA markers, namely aberrantly methylated DNA, are on the list of potential circulating tumor markers since the aberrant methylation of oncogenes and tumor suppressor genes is known to be one of the earliest events during tumor cell transformation, and it is efficiently detected in the abundance of normal, non-methylated DNA and apt to longer circulation in blood [ 2 , 3 ].…”

Mechanistic Effects of Estrogens on Breast Cancer

“…A potential tool to accomplish this is to measure mutated DNA in blood in patients. [135][136][137][138][139]…”

“…Accordingly, a major research focus should be on developing new, highly sensitive methods to detect these occult cancers and to determine their degree of aggressiveness. A potential tool to accomplish this is to measure mutated DNA in blood in patients 135–139 …”

Potential utility of miRNAs for liquid biopsy in breast cancer

“…The advancement of NGS and digital genomic approaches made biomarkers such as c-RNAs, circulating extracellular vesicles, tumor-educated platelets, proteins, etc. possible to detect in biofluids ( 71 , 75 , 76 ). Detection and identification of specific biomarkers are essential for the early diagnosis of BC and other cancers as they can provide additional insight into diagnosis, prognosis, and the response to treatment.…”