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From Blood to Bedside: A Review of Liquid Biopsy for Minimal Residual Disease and Recurrence Prediction in Early-Stage Breast Cancer

2025Open accessBenue State University

In plain language

Early-stage breast cancer carries a persistent risk of returning due to undetectable minimal residual disease, which conventional monitoring frequently misses. Liquid biopsy, particularly the analysis of circulating tumour DNA, presents a non-invasive method to identify residual disease and anticipate recurrence. Key testing platforms include digital droplet PCR, next-generation sequencing, and cancer personalised profiling by deep sequencing. These tools show high sensitivity and specificity at subclinical levels, identifying signs of relapse earlier than standard imaging or serum tests. Digital droplet PCR offers an affordable, precise approach for targeted mutations, whilst sequencing platforms deliver broader genomic coverage. Although these technologies support dynamic monitoring throughout diagnosis, treatment, and surveillance, routine clinical adoption still faces obstacles including high costs, lack of assay standardisation, and the need for validation across diverse populations.

Key takeaways

  • Liquid biopsy using circulating tumour DNA detects breast cancer recurrence earlier than conventional imaging or serum markers.
  • Digital droplet PCR delivers cost-effective and precise testing for targeted mutations, whereas sequencing methods offer comprehensive genomic coverage.
  • Circulating tumour DNA enables continuous monitoring across patient diagnosis, therapy, and post-treatment surveillance.
  • Widespread clinical integration is hindered by high assay costs, absent standardisation, and limited validation in diverse populations.

Why it matters

Conventional cancer surveillance often catches breast cancer relapse only after tumours have enlarged sufficiently to appear on scans. Detecting circulating tumour DNA in blood offers a sensitive, non-invasive method to recognise residual disease before symptoms emerge. This capability allows medical teams to intervene much earlier, tailor post-surgical therapies to individual risk, and potentially reduce recurrence rates.

Commercialisation angle

The findings are relevant to diagnostic laboratories, assay developers, and oncology clinics developing non-invasive disease monitoring tests. While platforms such as digital droplet PCR and next-generation sequencing are applied technologies, their routine commercialisation for minimal residual disease monitoring is at an intermediate stage, awaiting international assay standardisation, cost reductions, and large-scale validation trials across diverse populations.

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Abstract

Background Early-stage breast cancer carries a significant risk of recurrence due to undetectable minimal residual disease (MRD). Conventional surveillance lacks sensitivity for early relapse detection. Liquid biopsy, particularly circulating tumor DNA (ctDNA), offers a promising non-invasive strategy to detect MRD and predict recurrence.  Methods This review synthesizes recent evidence on liquid biopsy applications in early-stage breast cancer, with emphasis on MRD detection and recurrence monitoring. We evaluate key assay platforms—including digital droplet PCR (ddPCR), next- generation sequencing (NGS), and cancer personalized profiling by deep sequencing (CAPP-Seq)—and examine their clinical integration.  Results Liquid biopsy demonstrates high sensitivity and specificity in detecting ctDNA at subclinical levels, enabling earlier relapse prediction compared to imaging or serum markers. ddPCR offers affordability and precision for targeted mutations, while NGS and CAPP-Seq provide broader genomic coverage and adaptability. Integration into clinical pathways enables dynamic monitoring from diagnosis through treatment and surveillance. However, challenges remain, including assay standardization, cost, and validation across diverse populations.  Conclusion Liquid biopsy represents a paradigm shift in early-stage breast cancer management, enabling proactive monitoring and individualized treatment. Future priorities include global assay harmonization, large-scale validation trials, and in tegration of multi-omic and AI-based approaches to enhance predictive accuracy and clinical adoption.

Research topics

  • Cancer Genomics and Diagnostics
  • Breast Cancer Treatment Studies
  • BRCA gene mutations in cancer

Read the original research

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DOI: 10.38124/ijisrt/25oct1032

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