Despite significant advances in therapy, breast cancer continues to pose a high risk of recurrence, particularly among patients with early-stage disease who appear disease-free after treatment. Current follow-up strategies rely heavily on imaging and serum biomarkers, which often fail to detect microscopic residual disease. While tissue biopsies offer valuable insights, their invasive nature and limited repeatability prevent continuous monitoring of tumor evolution. Consequently, clinicians frequently become aware of relapse only after metastases have developed.
These limitations have spurred growing interest in liquid biopsy technologies, which enable cancer monitoring at the molecular level through a simple blood draw. In this context, there is an urgent need for minimal residual disease (MRD)-based strategies that allow earlier and more precise detection of breast cancer recurrence.
A new review published online on November 28, 2025, in Cancer Biology & Medicine (DOI: 10.20892/j.issn.2095-3941.2025.0431) by researchers from the Cancer Hospital of China Medical University and the Cancer Hospital of Dalian University of Technology highlights how MRD detection is reshaping breast cancer management. The article synthesizes clinical evidence, technological advances, and biological insights to demonstrate how circulating tumor DNA (ctDNA)-based MRD testing can identify residual disease, anticipate relapse, and guide personalized treatment decisions.
The review details two primary ctDNA-based MRD detection strategies. Tumor-informed approaches analyze a patient’s original tumor to design highly personalized assays capable of detecting ctDNA at extremely low levels, sometimes down to parts per million. These methods provide high specificity and allow clinicians to monitor tumor evolution and emerging resistance. Tumor-agnostic approaches, which use fixed gene or methylation panels, offer faster, more standardized testing with broader accessibility, albeit with slightly reduced sensitivity.
Clinical studies consistently show that ctDNA positivity after surgery strongly correlates with higher recurrence risk and shorter survival. Molecular relapse is often detected 8 to 15 months before it becomes visible on imaging. In the neoadjuvant setting, ctDNA dynamics closely mirror treatment response: early clearance predicts favorable outcomes, whereas persistent detection signals resistance. Importantly, recent trials indicate that MRD-guided treatment adjustments—such as switching endocrine therapy or intensifying targeted regimens—can significantly prolong progression-free survival. These findings position MRD not merely as a prognostic marker but as an active tool for personalized treatment decisions.
The authors emphasize that MRD fundamentally changes clinicians’ approach to relapse risk. “ctDNA allows us to detect cancer activity that imaging simply cannot capture,” they note. Early detection of molecular relapse creates a critical window for intervention when disease burden remains low. They caution, however, that careful implementation is essential, including assay standardization, establishing optimal thresholds, and defining appropriate testing intervals to avoid over- or under-treatment.
Looking ahead, MRD-guided monitoring promises to transform post-treatment breast cancer care. Patients with persistent ctDNA could benefit from early therapeutic escalation, while those who remain MRD-negative may avoid unnecessary toxicity. Beyond clinical practice, MRD also offers significant advantages for drug development and clinical trials by identifying high-risk populations and enabling earlier assessment of outcomes. As ctDNA technologies advance and costs decline, MRD testing is expected to transition from specialized centers to routine care, shifting breast cancer management from reactive detection to proactive, precision-driven intervention.
