Although advances in diagnosis and treatment have substantially improved outcomes for patients with early-stage breast cancer, several important unmet clinical needs remain. Conventional risk stratification based on clinicopathological characteristics lacks sufficient precision to accurately identify patients at genuine risk of recurrence, resulting in undertreatment of some high-risk patients and overtreatment of others. During neoadjuvant therapy, current assessment methods are also unable to detect treatment response at the molecular level early enough to guide timely therapeutic adjustments.Against this backdrop, minimal residual disease (MRD) testing has emerged as a promising molecular tool. With its non-invasive nature and high sensitivity, MRD offers a novel approach to recurrence risk stratification, dynamic treatment monitoring, and individualized therapeutic decision-making in early breast cancer.
During the 2026 Beijing Breast Cancer Forum and Beijing Breast Reconstruction Forum, held from June 23 to 28, 2026, Oncology Frontier interviewed Professor Miao Liu from Peking University People’s Hospital, who shared her perspectives on the clinical applications of MRD testing in early breast cancer, optimal testing strategies, its value in treatment decision-making, and future directions in clinical and translational research.
Q1. Oncology Frontier: In your opinion, what are the most mature clinical applications of MRD in breast cancer today?
Professor Miao Liu:
Minimal residual disease (MRD) has accumulated the strongest body of clinical evidence in advanced breast cancer, where patients typically have a higher tumor burden, experience disease events more frequently, and require continuous disease monitoring throughout treatment.
Several landmark studies—including SERENA-6 and PADA-1—have focused on metastatic breast cancer. For example, investigators in France used serial MRD monitoring to detect ESR1 mutations, allowing endocrine therapy to be adjusted according to evolving resistance mechanisms.
However, it is important to interpret these findings objectively. This year, the U.S. FDA did not incorporate MRD-guided monitoring or treatment switching into its recommendations for advanced breast cancer based on the available evidence, including results from the SERENA-6 study. This reflects the fact that MRD technology still faces technical and clinical implementation challenges and requires validation through larger studies with longer follow-up. Nevertheless, this should not diminish its considerable future clinical potential.
In early-stage breast cancer, MRD testing has increasingly been incorporated into neoadjuvant clinical trials to evaluate treatment response and guide both treatment escalation and de-escalation. At our center, we have already initiated neoadjuvant clinical studies that incorporate MRD testing to support response assessment and therapeutic decision-making.
Q2. Oncology Frontier: MRD testing can be performed using tumor-informed or tumor-agnostic approaches, as well as whole-genome or hotspot mutation panels. Should the testing strategy be individualized?
Professor Miao Liu:
MRD testing offers important advantages, including its minimally invasive nature and high analytical sensitivity. Traditionally, treatment decisions have relied primarily on imaging and pathological assessments. However, these methods generally detect recurrence only after lesions become radiologically visible and therefore cannot provide the early warning that patients and clinicians desire.
Currently, MRD testing can be broadly categorized into tumor-informed and tumor-agnostic approaches, each with distinct strengths and limitations.
Tumor-informed assays require tumor tissue for analysis and are typically based on whole-genome sequencing (WGS) or whole-exome sequencing (WES). These approaches provide broader genomic coverage, greater sequencing depth, and higher analytical precision, making them the most widely adopted strategy in contemporary clinical trials. However, they are associated with higher costs and longer turnaround times, limiting their accessibility for long-term serial monitoring.
By contrast, tumor-agnostic assays do not require tumor tissue and rely solely on peripheral blood samples. They offer shorter reporting times and lower costs, making them particularly attractive for longitudinal monitoring in patients with advanced disease, without requiring invasive biopsies of metastatic lesions.
However, tumor-agnostic assays generally focus on predefined panels of known cancer-associated hotspot mutations. Consequently, their genomic coverage is more limited, and their specificity is generally lower than that of tumor-informed approaches. Some clinical studies have also reported higher circulating tumor DNA (ctDNA) positivity rates with these assays.
Q3. Oncology Frontier: What are the greatest challenges to using MRD-guided treatment escalation or de-escalation in clinical practice? How close are we to incorporating MRD into routine clinical decision-making?
Professor Miao Liu:
To date, MRD has been used predominantly in advanced breast cancer, where rapid disease progression and frequent clinical events make it particularly valuable for dynamic monitoring and treatment adjustment.
In early-stage breast cancer, the introduction of targeted therapies, immunotherapy, and adjuvant CDK inhibitors has significantly improved patient outcomes. Nevertheless, one of the major unresolved clinical challenges is identifying which patients truly require intensified adjuvant therapy and which are likely being overtreated.
MRD provides a valuable molecular perspective that complements conventional clinicopathological prognostic factors. By detecting residual tumor-derived DNA fragments in the bloodstream, MRD may help identify patients who are most likely to benefit from treatment intensification.
However, whether MRD alone can reliably support routine clinical decision-making remains uncertain. Additional high-quality clinical evidence is still needed before MRD can be fully integrated into standard practice.
Q4. Oncology Frontier: What do you see as the most important future directions for clinical and translational MRD research in breast cancer? Do you expect future randomized controlled trials to incorporate MRD-guided precision treatment strategies?
Professor Miao Liu:
For MRD to become part of routine clinical practice, we need robust evidence from large, randomized Phase III clinical trials. At present, evidence supporting MRD-guided treatment interventions in early breast cancer remains limited.
Because triple-negative breast cancer (TNBC) has the poorest prognosis among breast cancer subtypes, it was the first to undergo extensive investigation. However, clinical trials evaluating MRD-guided treatment intensification with immunotherapy have produced negative results.
Studies involving luminal breast cancer and HER2-positive disease have generally been limited by relatively small sample sizes and short follow-up durations. Although these studies have demonstrated encouraging trends regarding MRD’s value in recurrence prediction and treatment optimization, the evidence remains insufficient. Larger, rigorously designed Phase III trials are urgently needed to validate these findings.
Beyond generating stronger clinical evidence, continued improvements in the technology itself will also be essential. Both the sensitivity and accuracy of MRD assays require further refinement, while testing costs remain a major barrier to widespread implementation.
Fortunately, sequencing technologies continue to evolve rapidly. When WGS and WES were first introduced, they cost tens of thousands of yuan per patient. As sequencing platforms have matured and become more widely available, costs have declined dramatically.
The same trend is expected for NGS-based ctDNA MRD testing. Although current testing remains relatively expensive, continued technological advances and broader adoption should substantially reduce costs over time, making large Phase III studies more feasible and ultimately facilitating broader clinical implementation.
Professor Miao Liu
Peking University People’s Hospital
