Liquid Biopsy for Early Detection of Breast Cancer: Evidence and Public Health Implications from a Systematic Review

Abstract

Objective: To assess how well liquid biopsy technologies work for early breast cancer detection and how they may be included in cancer control and public health screening initiatives.

Methods: A thorough search of Web of Science, PubMed, Embase, and Scopus was done to locate research articles released between January 2015 and August 2025. Exosomes, circulating tumor cells (CTCs), or circulating tumor DNA (ctDNA) were tested in eligible studies as liquid biopsy biomarkers for the early detection of breast cancer in individuals who were asymptomatic or in the early stages of the disease. The study’s quality was assessed by two reviewers who independently screened, extracted data, and followed PRISMA and QUADAS-2 recommendations.

Findings: A total of forty-three (43) studies satisfied the requirements for inclusion. The majority concentrated on ctDNA tests, such as methylation signatures and mutation profiling. Specificities were usually above 90%, whereas reported sensitivities varied from 60% to 98%. Exosome-based methods and CTC assays offered supplementary diagnostic utility. New multi-omic systems decreased false positives and enhanced stage I detection. Ultra-sensitive ctDNA tests have been shown in recent research to be able to identify relapses up to 38 months prior to a clinical recurrence. However, few research were conducted in low- and middle-income countries (LMICs), and cost-effectiveness assessments were scarce.

Conclusion: One promising minimally invasive method for the early diagnosis of breast cancer is liquid biopsy. Especially in LMICs with limited access to mammography, its incorporation into public health screening programmes could increase equity and decrease diagnostic delays. To promote fair worldwide acceptance, extensive prospective trials, health economic analyses, and implementation studies are desperately needed.