Advancing Early Detection and Management of Triple-Negative Breast Cancer: A Systematic Review of Liquid Biopsy Applications
Advancing Early Detection and Management of Triple-Negative Breast Cancer: A Systematic Review of Liquid Biopsy Applications
Elham Khakshour,1,*Mahsa Asghari,2Mohammad Amin Shahram,3Soroush Mohammadi,4
1. Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran 2. Vasei Clinical Research Development Unit in Sabzevar University of Medical Sciences, Sabzevar, Iran 4. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Science, Mashhad, Iran
Introduction: Triple-negative breast cancer (TNBC) is a particularly aggressive form of breast cancer with the absence of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. The lack of targeted therapies leads to its poor prognosis and limited treatment options. Due to rapid progression and high metastasis rate in TNBC, early detection is crucial for improving its outcomes. Liquid biopsy, a non-invasive diagnostic tool that analyzes biomarkers such as circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), offers a promising approach for early detection and management of TNBC. This systematic review aims to evaluate the role of liquid biopsy in the early detection of TNBC, focusing on the effectiveness of ctDNA and CTCs in identifying the disease at an early stage, monitoring disease progression, and guiding personalized treatment.
Methods: This systematic review was conducted by searching multiple databases, including PubMed, Embase, and Cochrane Library, for studies published between 2015 and 2024. Included studies were selected based on the following criteria: (1) clinical trials, observational studies, meta-analyses, and systematic reviews evaluating the application of liquid biopsy in TNBC, (2) research focusing on ctDNA and CTCs detection methods, and (3) studies reporting on diagnostic accuracy, prognostic value, and early detection capabilities. Exclusion criteria comprised case reports, case series, and studies not focused on TNBC or lacking relevant outcome data.
Results: The review analyzed 25 studies involving 1,200 TNBC patients. Findings revealed that liquid biopsy is highly effective for early-stage detection of TNBC. Sensitivity rates for ctDNA detection ranged from 60% to 85%, while specificity varied from 70% to 90%, depending on the detection method and the tumor’s genetic profile. Studies using digital PCR and next-generation sequencing (NGS) demonstrated higher sensitivity compared to the conventional methods. CTCs were also detected in early-stage TNBC patients, with sensitivity ranging from 50% to 75%. The presence of CTCs correlated strongly with a higher risk of metastasis and poorer prognosis. Additionally, liquid biopsy proved valuable in monitoring minimal residual disease (MRD) after treatment, with ctDNA levels serving as an early indicator of potential recurrence. The ability to identify actionable mutations through liquid biopsy facilitated personalized treatment approaches, although the effectiveness varied based on the tumor’s molecular characteristics and the technology used.
Conclusion: Liquid biopsy represents a significant advancement in the early detection and management of TNBC. The ability to detect ctDNA and CTCs provides a non-invasive method for identifying the disease at the early stages, which is crucial for improving patient outcomes. The review highlights the effectiveness of ctDNA analysis in detecting TNBC-specific mutations and monitoring disease progression, with higher sensitivity and specificity observed with advanced techniques such as digital PCR and NGS. CTC detection also offers valuable prognostic information, correlating with metastatic risk and treatment response. Despite its promising potential, challenges remain in standardizing liquid biopsy methods and improving sensitivity, particularly for early-stage disease. Further research and technological advancements are essential to overcome these challenges and integrate liquid biopsy into routine clinical practice. Overall, liquid biopsy shows great promise for enhancing early detection, personalizing treatment, and improving the management of TNBC, offering new hope for patients with this aggressive cancer subtype.