Seeing the invisible: Minimal residual disease opens a new window in breast cancer care

Breast cancer relapse often begins long before it can be seen. Tiny clusters of residual tumor cells may persist after treatment, quietly driving recurrence while remaining invisible to conventional imaging. This review highlights how minimal residual disease (MRD), detected through circulating tumor DNA (ctDNA) in blood, is changing that reality. By capturing molecular traces of cancer at extremely low levels, ctDNA-based monitoring can reveal relapse risk months ahead of clinical symptoms. The approach marks a shift from passive surveillance to early, precision-guided intervention, offering clinicians a new opportunity to identify high-risk patients, adjust treatment strategies in real time, and potentially stop metastasis before it takes hold.

Despite major therapeutic advances, breast cancer remains prone to recurrence, particularly in patients with early-stage disease who appear disease-free after treatment. Follow-up care still relies largely on imaging and serum markers, tools that struggle to detect microscopic disease. Tissue biopsies provide valuable information but are invasive and cannot be repeated frequently, nor can they track tumor evolution over time. As a result, clinicians are often alerted to relapse only after metastases are established. These gaps have driven interest in liquid biopsy technologies that can monitor cancer at the molecular level through a simple blood draw. Based on these challenges, there is a pressing need to develop minimal residual disease (MRD)-based strategies that enable earlier, more precise monitoring of breast cancer recurrence.

In the review published (DOI: 10.20892/j.issn.2095-3941.2025.0431)online on November 28, 2025, researchers from the Cancer Hospital of China Medical University and the Cancer Hospital of Dalian University of Technology examine how minimal residual disease detection is reshaping breast cancer management. Published in Cancer Biology & Medicine, the article brings together clinical evidence, technological advances, and biological insights to show how ctDNA-based MRD testing can detect residual disease, anticipate relapse, and guide treatment decisions. The review positions MRD monitoring as a key step toward more adaptive, precision-oriented breast cancer care.

The review outlines two major ctDNA-based MRD detection strategies. Tumor-informed approaches analyze a patient's original tumor to design personalized assays capable of detecting ctDNA at extremely low levels, sometimes down to parts per million. These methods offer high specificity and allow clinicians to follow tumor evolution and emerging resistance. Tumor-agnostic approaches, which rely on fixed gene or methylation panels, trade some sensitivity for speed, standardization, and broader accessibility.

Across multiple clinical studies, ctDNA positivity after surgery consistently signals a dramatically higher risk of recurrence and shorter survival. In many cases, molecular relapse is detected 8 to 15 months before radiographic evidence appears. In the neoadjuvant setting, ctDNA dynamics closely track treatment response: early clearance predicts favorable outcomes, while persistent detection suggests resistance. Importantly, recent trials show that MRD-guided treatment adjustments—such as switching endocrine therapies or intensifying targeted regimens—can significantly extend progression-free survival. Together, these findings support MRD not just as a prognostic marker, but as an active decision-making tool that bridges the gap between standard treatment protocols and individualized care.

According to the authors, MRD detection fundamentally changes how clinicians think about relapse risk. “ctDNA allows us to detect cancer activity that imaging simply cannot capture,” they explain. By revealing molecular relapse early, MRD monitoring opens a critical window for intervention, when disease burden is still low. At the same time, the authors stress the importance of careful implementation, noting that assay standardization, optimal thresholds, and appropriate testing intervals must be clearly defined to avoid over- or under-treatment.

Looking ahead, MRD-guided monitoring could redefine post-treatment care in breast cancer. Patients with persistent ctDNA may be candidates for early therapeutic escalation, while those who remain MRD-negative could safely avoid unnecessary toxicity. Beyond clinical practice, MRD offers powerful advantages for drug development and clinical trials by identifying high-risk populations and enabling earlier outcome assessment. As technologies mature and costs decline, ctDNA-based MRD testing is expected to move from specialized settings into routine care, shifting breast cancer management from delayed detection toward timely, precision-driven intervention.

###

References

DOI

10.20892/j.issn.2095-3941.2025.0431

Original Source URL

https://doi.org/10.20892/j.issn.2095-3941.2025.0431

Funding information

This work was supported by the National Natural Science Foundation of China (Grant No. 82373113, XJ), Shenyang Breast Cancer Clinical Medical Research Center (Grant No. 2020-48-3-1, ST), Shenyang Public Health R&D Special Project (Grant No. 22-321-31-04, ST), and Liaoning Revitalization Talents Program (Grant No. XLYC1907160, XJ).

About Cancer Biology & Medicine

Cancer Biology & Medicine (CBM) is a peer-reviewed open-access journal sponsored by China Anti-cancer Association (CACA) and Tianjin Medical University Cancer Institute & Hospital. The journal monthly provides innovative and significant information on biological basis of cancer, cancer microenvironment, translational cancer research, and all aspects of clinical cancer research. The journal also publishes significant perspectives on indigenous cancer types in China. The journal is indexed in SCOPUS, MEDLINE and SCI (IF 8.4, 5-year IF 6.7), with all full texts freely visible to clinicians and researchers all over the world (http://www.ncbi.nlm.nih.gov/pmc/journals/2000/).