DOI: https://doi.org/10.36719/3104-4700/4/4-14

Liquid Biopsy and Circulating Tumor DNA for Monitoring Minimal Residual Disease in Hormone Receptor-Positive Breast Cancer: Current Evidence, Technologies, Clinical Outcomes, and Future Directions

Gulnar Abdulhasanova

Abstract. Background. Minimal residual disease (MRD) drives late relapse and mortality in hormone receptor-positive (HR+) breast cancer. Conventional surveillance modalities—serum tumor markers and cross-sectional imaging—lack sufficient sensitivity to detect MRD at a clinically actionable stage. Objective. This review synthesizes evidence on liquid biopsy and circulating tumor DNA (ctDNA) for MRD monitoring in HR+ breast cancer, covering assay technologies, clinical trial findings, methodological limitations, and future research priorities. Evidence Base. Evidence derives from systematic reviews, meta-analyses, prospective and retrospective cohorts, and interventional trials (PADA-1, SERENA-6) published between 2018 and 2026, as identified through the Scopus AI analytical platform. Key Findings. ctDNA-based MRD assays detect recurrence a median of 5–14 months before clinical or radiographic manifestation, with individual cases reporting a lead time of up to five years. Tumor-informed mutation-based assays achieve sensitivity of 50–79% with specificity approaching 100%. Methylation-based assays demonstrate sensitivity of 62.5% and specificity of 100%, outperforming mutation-based approaches in early-stage, low-shedding HR+ tumors. ctDNA dynamics correlate with progression-free and overall survival. The SERENA-6 trial demonstrated improved PFS and quality of life with ctDNA-guided early endocrine switching; the PADA-1 trial showed ctDNA dynamics predict PFS and OS, with ctDNA-based risk models outperforming clinical parameters. Conclusion. Despite robust prognostic evidence, assay standardization deficits, clonal hematopoiesis-related false positives, and cost barriers preclude routine clinical adoption. Large-scale, prospective, randomized trials are urgently required.

Keywords: liquid biopsy, circulating tumor DNA (ctDNA), minimal residual disease (MRD), hormone receptor-positive (HR+) breast cancer, tumor-informed assay, methylation-based assay, ESR1 mutation, clonal hematopoiesis, PADA-1, SERENA-6