An Overview of Circulating Cell-Free Nucleic Acids in Diagnosis and Prognosis of Triple-Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer due to its molecular heterogeneity and poor clinical outcomes. Analysis of circulating cell-free tumor nucleic acids (ctNAs) can improve our understanding of TNBC and provide efficient and non-invasive clinical biomarkers that may be representative of tumor heterogeneity. In this review, we summarize the potential of ctNAs to aid TNBC diagnosis and prognosis. For example, tumor fraction of circulating cell-free DNA (TFx) may be useful for molecular prognosis of TNBC: high TFx levels after neoadjuvant chemotherapy have been associated with shorter progression-free survival and relapse-free survival. Mutations and copy number variations of TP53 and PIK3CA/AKT genes in plasma may be important markers of TNBC onset, progression, metastasis, and for clinical follow-up. In contrast, the expression profile of circulating cell-free tumor non-coding RNAs (ctncRNAs) can be predictive of molecular subtypes of breast cancer and thus aid in the identification of TBNC. Finally, dysregulation of some circulating cell-free tumor miRNAs (miR17, miR19a, miR19b, miR25, miR93, miR105, miR199a) may have a predictive value for chemotherapy resistance. In conclusion, a growing number of efforts are highlighting the potential of ctNAs for future clinical applications in the diagnosis, prognosis, and follow-up of TNBC.

Unlocking the Potential of Circulating miRNAs in the Breast Cancer Neoadjuvant Setting: A Systematic Review and Meta-Analysis

“…This was observed for miRNAs that were detected at baseline and at different time points. Nevertheless, these pooled results included different circulating miRNAs, diverse types of samples, and a heterogeneous BC population, which might have influenced the magnitude of the overall effect size since the consideration of molecular subtype is crucial in determining specific miRNAs’ predictive and prognostic value [ 74 , 75 , 76 , 77 ]. In addition, specific miRNAs’ level patterns may influence a predictive biomarker’s ability to predict a therapeutic response [ 27 , 78 ].…”

Next-Generation Sequencing and Triple-Negative Breast Cancer: Insights and Applications

“…Liquid biopsies refer to different body fluids, such as blood or urine, with different RNA or DNA sources: circulating tumor cells (CTCs), exosomes, and circulating cell-free nucleic acids (cfNAs). These components allow for the real-time monitoring of tumor progression using a non-invasive method [97]. In this review, NGS sequencing was performed on the plasma from a total of 310 TNBC patients in six studies.…”

Plasma Circular RNAs as Biomarkers for Breast Cancer

“…Similarly, clinical research needs to discover innovative biomarkers to predict tumor progression and response to treatment, which could lead to effective therapeutic targets. From this point of view, liquid biopsies represent an attractive tool, as they can be easily standardized in routine clinical practice [2,3]. In recent years, the use of liquid biopsies has become particularly interesting for the detection of circular RNAs (circRNAs), a class of non-coding RNAs (ncRNAs) that are attracting increasing attention as modulators of gene expression through interaction with DNA, miRNAs, and proteins.…”