Editor’s Note: In breast cancer treatment, the use of neoadjuvant therapy has become increasingly widespread, and its concepts continue to evolve—from traditional treatment models to today’s focus on individualized care and a holistic approach—improving patient survival. Professor Qiang Liu from Sun Yat-sen Memorial Hospital of Sun Yat-sen University has long focused on optimizing neoadjuvant strategies for early breast cancer, using circulating tumor DNA (ctDNA) to enhance evaluation and monitoring, and proposing the concept of Systemic Tumor Burden (STB). At the 2025 CSCO Annual Meeting, Professor Liu delivered a keynote lecture titled 'New Perspectives on Neoadjuvant Therapy for Breast Cancer: Those Who Fail to See the Whole Cannot Govern the Parts' and shared further insights with Oncology Frontier, highlighting the shift from population-level to individualized treatment and from local to systemic thinking.From “Blind Box” to “Scientific Fortune-Telling” to “Changing Destiny”
At this year’s CSCO breast cancer session, I delivered a talk titled ‘New Perspectives on Neoadjuvant Therapy for Breast Cancer: Those Who Fail to See the Whole Cannot Govern the Parts.’ Neoadjuvant therapy is now widely applied, especially in HER2-positive and TNBC patients, and increasingly in HR+/HER2− disease. In our center, over 30% of 4,000–5,000 annual cases receive neoadjuvant therapy first. Traditionally, surgery was performed first, followed by adjuvant therapy, since surgery was seen as the main curative approach. The ‘new’ in neoadjuvant therapy refers to changing the order of treatment, administering systemic therapy before surgery, and adjusting the subsequent plan based on response. Relying solely on surgery no longer improves cure rates, and giving systemic therapy preoperatively allows real-time evaluation of tumor response, enabling personalized adjustments. I often compare adjuvant therapy to ‘opening a blind box’—we only know the outcome after recurrence. With neoadjuvant therapy, we can predict treatment response early and adjust accordingly, potentially improving survival. Multiple phase III trials confirm the value of neoadjuvant therapy in TNBC and HER2-positive disease. It not only predicts outcomes (‘scientific fortune-telling’) but also allows ‘changing destiny’ through treatment modification.
“Mock Exams” Are Not the “Final Exam”
Neoadjuvant therapy assesses systemic therapy by observing local tumor response, but local response does not fully represent systemic disease. Neoadjuvant therapy is like a mock exam—it provides valuable information, but the ultimate goal is cure, the ‘final exam.’ Even perfect response (pCR) does not guarantee no recurrence, and failure to reach pCR does not mean inevitable treatment failure. With treatment adjustments, patients who fail to achieve pCR still have a 60–70% five-year survival rate. The key is to use this ‘mock exam’ to refine therapy and maximize cure rates.
From TNM Staging to STB Staging
Breast cancer is generally considered systemic, but not all cases behave the same. Historical data (DBCG77 trial) showed that 40–50% of high-risk patients achieved long-term survival with surgery alone. Recent studies, including a JAMA report, suggest some early TNBC patients can avoid chemotherapy without compromising distant-metastasis-free survival. ctDNA technology now allows precise identification of patients likely to metastasize. Our Nature Communications study demonstrated that combining ctDNA thresholds with Systemic Tumor Burden (STB) modeling can identify low-risk patients who may avoid overtreatment even without pCR. Baseline ctDNA negativity had strong predictive value for favorable outcomes. Conversely, ctDNA positivity post-surgery or chemotherapy predicts high recurrence risk and indicates the need for treatment intensification. Integrating multiple time points, the STB model offers an accurate risk stratification tool to distinguish high-risk from low-risk patients and guide timely, individualized treatment decisions.
“Introverted” vs. “Extroverted” Tumors: The Case for Individualized Treatment
One patient once said to me, ‘Professor Liu, for you it may be 70%, 80%, or 90% cure rate, but for me it’s either 0% or 100%.’ This perfectly illustrates why treatment must be individualized. Some patients with extensive nodal disease and high Ki-67 but negative ctDNA respond well to minimal therapy and remain disease-free, while others with early-stage, low-risk tumors relapse quickly. We classify tumors as ‘introverted’ (aggressive locally but less likely to metastasize) or ‘extroverted’ (prone to early spread). STB modeling may help distinguish these and guide treatment de-escalation or intensification. Neoadjuvant therapy is a critical first step in individualized care, but clinicians must keep the big picture in mind—focusing not only on local response but on systemic control. In 2020, our JCO Precision Oncology paper (selected as one of ASCO’s Top 5 most popular articles) highlighted a case where the local tumor shrank, but ctDNA levels rose, and metastasis occurred 21 months later. Today, with tools like STB staging, we can better separate local from systemic disease and deliver more precise, personalized treatment strategies. I believe STB staging may lead the next revolution in early breast cancer management.
About the Expert
Prof. Qiang Liu Chief of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University Executive Vice President, Yixian Breast Tumor Hospital Director, Breast Tumor Center and Department of Breast Surgery Chief Physician, Professor, Senior Researcher, Ph.D. Supervisor
