Editor's Note: From December 10 to 13, 2024, the 47th San Antonio Breast Cancer Symposium (SABCS) took place in San Antonio, USA. As one of the largest and most prestigious scientific gatherings in the field of breast cancer research, SABCS showcased the latest findings, clinical practices, treatment advancements, and technological innovations from the past year.Among the many noteworthy contributions, a study by Dr. Yunjian Liu's team from The Fourth Hospital of Hebei Medical University stood out. Their research focused on the prognostic value of ctDNA monitoring in breast cancer patients undergoing neoadjuvant therapy and was presented as a poster (Abstract No. P3-05-22). The study highlights how personalized ctDNA testing can dynamically monitor minimal residual disease (MRD), predict treatment efficacy and recurrence risk, and provide valuable insights for clinical decision-making. Oncology Frontier interviewed Professor Liu onsite for an in-depth discussion.

Oncology Frontier: Can you elaborate on the “OriMIRACLES-MRD” detection method mentioned in your study? How does it aid in monitoring ctDNA in breast cancer patients?

Dr. Yunjian Liu:As we all know, the San Antonio Breast Cancer Symposium is an annual highlight in the breast cancer research community. Over the years, our team has consistently presented our findings at this conference. This year was particularly remarkable, as Chinese researchers not only contributed multiple poster presentations but also delivered oral reports, including those by Academician Binghe Xu and Professor Junjie Li, which were especially noteworthy.

Our study focuses on a personalized ctDNA detection approach for stage II-III breast cancer patients, utilizing whole-genome exome sequencing technology. In collaboration with Zhijin Medical, we developed individualized panels tailored to each patient’s unique genetic variations. By tracking these mutations before, during, and after neoadjuvant therapy (NAT), as well as during postoperative follow-up, we aim to better understand their clinical implications.

For instance, if certain gene mutations are identified during the initial testing and persist in subsequent monitoring, they may have significant clinical value. In our study, baseline testing before NAT revealed ctDNA positivity in 92% of patients. While the specific significance of some mutations remains unclear, their presence alone warrants attention.

During the study, we conducted ctDNA testing at three key intervals: after 2–3 cycles of NAT, post-surgery, and throughout follow-up. The individualized design of each panel reflects the core principle of personalized medicine, addressing the distinct genetic variation profiles of each patient.

Oncology Frontier: Your study found a 92% ctDNA positivity rate at baseline. What implications does this have for early diagnosis and treatment of breast cancer?

Dr. Yunjian Liu: As mentioned, 92% of patients showed ctDNA positivity during baseline testing before NAT. However, the clinical significance of many of these mutations remains uncertain. While they hold limited value for early diagnosis, they are highly useful for monitoring treatment progress and assessing prognosis.

Our study included diverse breast cancer subtypes, such as triple-negative and HER2-positive cancers, all in stage II-III requiring NAT. Given their higher tumor burden, the likelihood of detecting genetic mutations is naturally greater. Although the diagnostic utility of these mutations is limited, their role in monitoring treatment response and predicting prognosis is substantial.

Oncology Frontier: Your research indicates that patients with persistent ctDNA positivity after NAT failed to achieve pCR. Does this suggest ctDNA testing could serve as an effective marker for treatment evaluation? Could it be integrated into routine clinical monitoring in the future?

Dr. Yunjian Liu: We analyzed samples from 28 patients and conducted over 100 gene mutation tests. Our findings revealed that patients who responded well to treatment—such as HER2-positive patients receiving targeted therapy—showed a gradual clearance of MRD, often achieving pCR. Conversely, patients with persistent MRD positivity were unable to achieve pCR, and postoperative follow-up linked persistent MRD to a higher risk of early recurrence.

For example, one patient with HR-positive, HER2-positive breast cancer initially refused chemotherapy and opted for endocrine therapy. Her MRD remained positive throughout this period. After accepting a neoadjuvant regimen combining anti-HER2 therapy with chemotherapy, her MRD turned negative, and no metastases were detected post-surgery. Over a year into follow-up, the patient remains recurrence-free with excellent treatment outcomes.

However, in some patients with persistent MRD positivity, the tumor was not entirely eradicated during NAT (non-pCR). These patients experienced persistent MRD during follow-up, suggesting poor prognosis and an increased risk of recurrence or metastasis.

Given our small sample size, we plan to expand the study to validate these findings further. We believe this method will become a valuable tool in the era of precision medicine, enabling personalized and precise monitoring of treatment efficacy and recurrence risks. This would undoubtedly improve outcomes for breast cancer patients.

About Dr. Yunjian Liu

Yunjian Liu, MD, PhD

• Second-Class Professor and Doctoral Supervisor
• Recognized as an Outstanding Young and Middle-Aged Expert in Hebei Province
• Lead of the Key Discipline in Surgery (Category A) in Hebei Province
• Director, Key Laboratory of Tumor Microenvironment and Drug Resistance in Hebei Province
• Vice Chair, Breast Disease Committee, Chinese Association of Medical Education
• Executive Vice Chair, Health Science Committee, Chinese Health Management Association
• Standing Member, Breast Cancer Expert Committee, Chinese Society of Clinical Oncology (CSCO)
• Standing Member, Tumor Plastic Surgery Committee, Chinese Anti-Cancer Association
• Standing Member, Breast Cancer Committee, Chinese Anti-Cancer Association
• Member, Breast Group, Chinese Medical Association Surgery Branch
• Standing Member, Breast Surgery Specialist Committee, Chinese Medical Doctor Association
• Vice President and Secretary-General, Hebei Provincial Anti-Cancer Association
• Executive Chair, Hebei Provincial Cancer Prevention and Control Alliance
• President, Hebei Society of Mathematical Medicine

Professor Liu has made significant contributions to breast cancer research and treatment, focusing on surgical oncology and the development of innovative monitoring technologies. His work exemplifies the integration of cutting-edge science with clinical practice to enhance patient outcomes.