Despite improvements in breast cancer treatment, recurrence remains a significant concern, especially for patients with early-stage disease who seem free of cancer after therapy. Traditional follow-up methods such as imaging and serum markers often fail to detect small amounts of remaining disease. Tissue biopsies provide important information but are invasive and cannot be performed frequently or used to monitor changes in the tumor over time. As a result, relapses are often detected only after metastases have developed.
A review published online on November 28, 2025, in Cancer Biology & Medicine by researchers from the Cancer Hospital of China Medical University and the Cancer Hospital of Dalian University of Technology discusses how minimal residual disease (MRD) detection is changing breast cancer management. The article (DOI: 10.20892/j.issn.2095-3941.2025.0431) compiles clinical evidence and technological advances showing that circulating tumor DNA (ctDNA)-based MRD testing can identify residual disease, predict relapse, and inform treatment decisions.
The review describes two main ctDNA-based MRD detection strategies. Tumor-informed approaches use information from a patient’s original tumor to create personalized tests that can find ctDNA at very low levels, offering high specificity and allowing clinicians to track changes in the tumor and resistance to treatments. Tumor-agnostic approaches use standard gene or methylation panels, which may be less sensitive but are faster and more accessible.
Clinical studies consistently show that detecting ctDNA after surgery indicates a much higher risk of recurrence and shorter survival times. In many cases, molecular signs of relapse appear 8 to 15 months before they can be seen through imaging. In patients receiving neoadjuvant therapy, changes in ctDNA levels closely match treatment response: early disappearance predicts better outcomes while continued presence suggests resistance to therapy. Recent trials also indicate that adjusting treatment based on MRD status—such as changing endocrine therapies or increasing targeted treatments—can extend progression-free survival.
The authors state: "ctDNA allows us to detect cancer activity that imaging simply cannot capture." They note that early detection of molecular relapse with MRD monitoring provides an opportunity for intervention when the disease burden is still low. However, they emphasize the need for careful implementation regarding assay standardization, threshold settings, and testing intervals to avoid inappropriate treatment decisions.
Looking forward, MRD-guided monitoring could change post-treatment care for breast cancer patients by identifying those who might benefit from earlier therapeutic escalation or those who could avoid unnecessary treatments if they remain MRD-negative. Additionally, MRD testing could help drug development by identifying high-risk groups and enabling earlier assessment of outcomes in clinical trials. As technology improves and costs decrease, ctDNA-based MRD testing is expected to become part of routine care.
