The highly anticipated 19th St. Gallen Breast Cancer Conference (SGBCC) is taking place from March 12 to 15, 2025, in Vienna, Austria. This year, the conference features a special “Voice of China” session, where multiple CSCO BC breast cancer experts share clinical, basic, and translational research findings from China.Among them, Prof. Qiang Liu from Sun Yat-sen Memorial Hospital, Sun Yat-sen University delivered a compelling presentation titled “Dynamic ctDNA tracking stratifies individual relapse risk and facilitates precision treatment for early TNBC.” Following the session, Oncology Frontier had the privilege of speaking with Professor Liu to discuss his report, focusing on the latest advancements and future applications of ctDNA research.Oncology Frontier: At this year’s SGBCC “Voice of China” session, you presented a report on dynamic ctDNA monitoring for stratifying relapse risk and guiding precision treatment in early TNBC. Could you provide an overview of the theoretical foundation for using ctDNA to predict prognosis and guide stratified treatment? What key findings has your research team achieved?
Prof. Qiang Liu: As an essential biomarker in liquid biopsy, circulating tumor DNA (ctDNA) has demonstrated unique clinical value in breast cancer diagnosis and treatment, gaining increasing attention in recent years. The 2025 St. Gallen International Breast Cancer Conference has dedicated specific discussions to ctDNA, and in the “Voice of China” session, we also presented breakthrough research in this field.
Our team has been actively investigating ctDNA liquid biopsy in breast cancer for over a decade and has published two key studies that highlight its clinical application potential. The first study, published in JCO Precision Oncology in 2020, was recognized by the American Society of Clinical Oncology (ASCO) as one of the “Top 5 Most Popular Articles” in ASCO’s journals that year. A more recent study has been accepted for publication in Nature Communications, introducing a new paradigm for using dynamic ctDNA monitoring to assess relapse risk and guide treatment decisions in solid tumors.
From a clinical perspective, the primary cause of mortality in breast cancer is not the local tumor itself but early, undetectable systemic micrometastases. While modern surgical techniques effectively remove the primary tumor, traditional imaging is often unable to detect micrometastatic disease, which remains a major driver of recurrence and metastasis.
As tumor-derived DNA fragments released into the bloodstream, ctDNA surpasses the limitations of imaging by offering unprecedented sensitivity—with detection thresholds as low as one in ten thousand molecules or even higher. This allows real-time monitoring of systemic tumor burden in early breast cancer patients.
Notably, our team has uncovered a discrepancy between local tumor burden (LTB) and systemic tumor burden (STB) that is not reflected by traditional clinical TNM staging. Some early-stage patients with small localized tumors and no lymph node involvement may still test ctDNA-positive post-surgery, indicating high metastatic risk. Conversely, certain patients with more advanced disease, such as those with multiple lymph node involvement or a high Ki-67 index in TNBC, test ctDNA-negative, suggesting that even with reduced treatment intensity, they can achieve long-term remission. This finding suggests that traditional imaging and pathologic response evaluation, such as pCR rates in neoadjuvant therapy, may underestimate the independent prognostic value of systemic tumor burden.
Based on these findings, our team has proposed a dual-dimension treatment strategy. For patients with predominantly local tumor burden, typically reflected by ctDNA-negative status or very low ctDNA levels, treatment de-escalation strategies can be explored, including shortening chemotherapy duration or even omitting chemotherapy in selected cases. On the other hand, for patients with high systemic tumor burden, often reflected by ctDNA positivity or elevated ctDNA levels, systemic treatment should be intensified despite good local control to prevent recurrence and distant metastases.
This approach has already accumulated strong clinical evidence in triple-negative breast cancer (TNBC), where ctDNA is released earlier than in other subtypes, making it an ideal model for research. Similar trends are also emerging in other breast cancer subtypes. This strategy is now transforming traditional treatment paradigms, shifting the focus from local tumor control to systemic micrometastasis prevention through precision intervention. While visible tumors can be surgically removed, the “invisible enemy” of systemic micrometastases remains the primary threat to survival.
The current research priority is to develop an effective and precise dynamic monitoring framework that quantifies ctDNA fluctuations in relation to tumor regression rates and evaluates the clearance efficiency of different treatment regimens on both local and systemic tumor burden. Real-time adjustments in treatment strategy based on ctDNA dynamics will not only optimize clinical decision-making but also provide new research avenues to further explore the biological mechanisms of breast cancer.
Ultimately, integrating ctDNA tracking into early breast cancer management will enable a personalized, risk-stratified approach that moves beyond conventional staging methods, offering a new standard for precision oncology.
Oncology Frontier: This year’s SGBCC conference placed a strong focus on how to define study endpoints when incorporating ctDNA into clinical research. What is your perspective on this issue?
Prof. Qiang Liu: As ctDNA testing technology becomes increasingly integrated into clinical research design, its role as both a screening tool for patient selection and an efficacy assessment marker has drawn significant attention. However, it is essential to recognize that the ultimate validation of any new detection method must be based on actual patient benefit. For early-stage patients, this means achieving disease-free survival (DFS) and potential cure, while for advanced-stage patients, the goal is long-term disease control.
Although ctDNA detection offers significantly greater sensitivity than traditional methods, it is important to remain cautious of its limitations. False-positive and false-negative results, along with DNA fragments released by dying cancer cells, can complicate interpretation. Clinicians must always consider individual patient characteristics when assessing the clinical utility of ctDNA results.
Over the past decade, our research team has progressively developed key technical guidelines for dynamic ctDNA monitoring. Our latest findings highlight two crucial elements. The first is the clinical significance of different sampling time points—ctDNA obtained during the perioperative period, before and after neoadjuvant therapy, carries distinct prognostic value. The second is the importance of setting precise quantitative thresholds—only when ctDNA levels exceed a certain threshold can they reliably indicate metastatic risk. Notably, because apoptotic tumor cells continue to release DNA fragments, the timing of ctDNA testing must account for the impact of treatment on tumor cell status. Mastering these technical considerations is critical for accurately interpreting ctDNA signals and avoiding clinical misjudgments.
Oncology Frontier: In early breast cancer, a ctDNA-positive result could justify treatment intensification, but it also carries the risk of overtreatment. Based on current evidence, in what clinical scenarios is ctDNA already feasible for guiding treatment decisions?
Prof. Qiang Liu: The clinical application of ctDNA has evolved beyond simply guiding treatment intensification and is now advancing toward precision stratification. Our team has conducted a multicenter study demonstrating that systemic tumor burden (STB) modeling, based on comprehensive ctDNA monitoring before neoadjuvant chemotherapy, during the perioperative period, and at post-surgical follow-ups every three to six months, can effectively stratify recurrence risk in triple-negative breast cancer (TNBC).
Our study results indicate that among patients who achieved pathologic complete response (pCR) after neoadjuvant chemotherapy and had low systemic tumor burden (ctDNA-negative), the rate of distant metastasis was 0%. Even in patients who did not achieve pCR but remained ctDNA-negative (n=37), the distant metastasis rate was only 2.7%, significantly lower than predictions from traditional risk models. These findings suggest that approximately 50% of TNBC patients may be eligible for treatment de-escalation.
TNBC is often regarded as the most aggressive breast cancer subtype, with early-stage cure rates ranging between 70% and 80%, meaning nearly one in four patients still faces recurrence risk. Our team has pioneered a dual-dimension treatment strategy. For 35% of patients classified as high-risk (high systemic tumor burden and no pCR), we have launched a nationwide study involving 25 centers and over 600 enrolled cases. This study investigates innovative combination regimens to overcome chemotherapy resistance.
For low-risk patients, I previously discussed the findings from high-impact studies published in JAMA and JAMA Oncology last year, which provide compelling evidence that some TNBC patients may not require chemotherapy. . Building on this, we are designing a de-escalation strategy that integrates ctDNA with additional biomarkers, such as tumor-infiltrating lymphocytes (TILs). This approach ensures that high-risk patients receive adequate intervention, while low-risk patients avoid the unnecessary toxicities of overtreatment.
The clinical translation of the systemic tumor burden model has already shown significant promise. When ctDNA concentrations fall below a defined threshold, the negative predictive value exceeds 97%. However, the application of this model depends on precise timing and quantitative analysis to mitigate the risk of false positives caused by DNA release from dying cancer cells. Our research has led to a standardized technological framework, with patents pending, which could revolutionize the precision management of TNBC.
Oncology Frontier: What are the key areas of consensus and controversy regarding ctDNA as a prognostic tool for early breast cancer? What are your expectations for its future clinical application?
Prof. Qiang Liu: ctDNA detection technology has made breakthrough advancements in the global academic community in recent years, and its transformative potential was a key topic of discussion at this year’s St. Gallen International Breast Cancer Conference. While clinical acceptance in China still lags behind, international expert consensus recognizes its ability to redefine cancer management.
The core value of ctDNA lies in its ability to overcome the limitations of traditional imaging. By detecting tumor-derived DNA fragments circulating in the bloodstream, ctDNA provides a quantitative and precise assessment of systemic tumor burden (STB). I often describe systemic tumor burden as the “invisible enemy” of breast cancer—something that imaging cannot detect, yet fundamentally determines prognosis. The latest ctDNA technology functions like an early warning radar, making these “invisible enemies” visible. By tracking their biological signals in real time, treatment strategies can shift from blind defensive measures to targeted interventions, significantly improving therapeutic efficiency.
Despite its potential, several technical hurdles remain before ctDNA can be widely implemented in routine clinical practice. Standardization is a major challenge. Different detection platforms—such as NGS, digital PCR, tumor-informed methods, and tumor-naïve approaches—vary significantly in sensitivity and specificity, limiting cross-platform comparability. Additionally, optimal sampling time points remain debated, particularly for perioperative monitoring, neoadjuvant therapy response, and post-treatment surveillance. The ideal testing frequency—whether monthly, quarterly, or biannually—and its impact on clinical decision-making still require further evidence. High testing costs and interference from DNA released by dying cancer cells or clonal hematopoiesis mutations also pose barriers to large-scale clinical adoption.
Our team has achieved key breakthroughs in addressing these challenges. We have established the first standardized protocol for ctDNA dynamic monitoring in TNBC and clarified that baseline ctDNA levels, though frequently positive before treatment, do not have significant prognostic value. However, our research confirms that a negative baseline ctDNA result carries high predictive value. Among TNBC patients with negative baseline ctDNA, even those with later-stage clinical disease have shown no recurrence or metastasis, demonstrating that lymph node involvement does not necessarily correlate with hematogenous spread risk. These findings highlight the superiority of ctDNA over traditional TNM staging.
We have also introduced the concept of ctDNA thresholds, which has now been validated using I-SPY2 trial data. Our systemic tumor burden model, integrating multiple time points, allows for early risk stratification. This enables treatment de-escalation for low-risk patients while ensuring timely, intensified therapy for high-risk individuals. Our upcoming ctDNA-guided TNBC de-escalation trial will assess whether patients classified as low-risk by ctDNA profiling can safely reduce or omit chemotherapy, thus sparing them from unnecessary toxicity while maintaining oncologic safety.
As more evidence accumulates, we have every reason to believe that ctDNA technology will redefine the future of breast cancer precision medicine.
- Professor, Chief Physician, Researcher, PhD Supervisor
- Chair of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University
- Executive Vice President, Yixian Breast Cancer Hospital; Director, Breast Cancer Center; Director, Breast Surgery
- Member, ESO-ESMO International Consensus Panel on Young Breast Cancer
- Standing Member and Deputy Secretary-General, CSCO Breast Cancer Committee
- Standing Member, Breast Cancer Committee, Chinese Anti-Cancer Association
- Standing Member, Molecular Medicine Committee, Chinese Anti-Cancer Association
- Chair, Guangdong Breast Disease Society
- Associate Editor, Chinese Journal of General Surgery; Deputy Editor, Chinese Journal of Endocrine Surgery
- Former Lecturer at Dana-Farber Cancer Institute, Harvard Medical School
- Principal Investigator of multiple national projects on liquid biopsy and immunotherapy in breast cancer
- Lead author of China’s first Young Breast Cancer Consensus Guidelines
- Recipient of the 2020 “National Distinguished Physician” Award by People’s Daily
