Editor's Note: From January 5-6, 2024, the "Northern Breast Cancer Salon Annual Review and 2024 CSCO BC Guidelines Update Discussion" was held in Beijing. During the session on "Targeted Treatment-TNBC," Professor Qiang Liu from Sun Yat-sen Memorial Hospital of Sun Yat-sen University presented a report on "Progress in the Treatment of Early Triple-Negative Breast Cancer (TNBC)." After the session, "Oncology Frontier" conducted an exclusive interview with Professor Liu on the treatment of patients with early TNBC. The detailed content is organized below.01
Oncology Frontier : Triple-negative breast cancer (TNBC) is considered the “most aggressive” subtype of breast cancer. Could you briefly introduce us to the current diagnosis and treatment status of early TNBC and the challenges faced?
Professor Qiang Liu : TNBC lacks clear therapeutic targets and has a high risk of recurrence and death in the short term. Data from a study in the USA shows that within the first two years of diagnosis, the mortality rate for TNBC patients is 8-11 times higher than that for hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer patients. Many TNBC patients also experience recurrence and metastasis within two years of diagnosis. Once metastasis occurs, it predominantly affects visceral organs: 40% of patients develop lung metastases, 20% liver metastases, and 30% brain metastases. Once systemic metastasis occurs, the median overall survival is only 15-18 months. Therefore, compared to other subtypes, TNBC is more challenging to treat, which also imposes significant psychological stress on patients. However, the overall treatment outcomes for early-stage TNBC patients are quite good, with a cure rate over 75%. Nevertheless, more than 20% of patients may still experience recurrence and metastasis, and the clinical challenge lies in identifying those at high risk.
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Oncology Frontier : At the 2023 ESMO conference, the 5-year EFS results of the KEYNOTE-522 study were announced, giving us great confidence in treatment. Besides the KEYNOTE-522 study, what other research in the field of early TNBC treatment do you believe can provide more confidence?
Professor Qiang Liu : Traditional chemotherapy methods have struggled to further improve the survival rates of TNBC patients, hence numerous immunotherapy studies have been conducted in this area (such as GeparNuevo, KEYNOTE-522, IMpassion 130, IMpassion 031, and ALEXANDRA/IMpassion030). These studies have yielded both positive and negative results. At the 2023 SABCS conference, the ALEXANDRA/IMpassion030 study reported negative results, which, after extensive discussion, was attributed to the enrolled patients having low tumor burden, making traditional treatments sufficient, thus failing to showcase the benefits of immunotherapy in this study. GeparNuevo, however, is an intriguing study where patients receiving neoadjuvant therapy did not see a significant improvement in pathological complete response (pCR), but long-term follow-up revealed a dramatic improvement in invasive disease-free survival (iDFS), distant disease-free survival (DDFS), and overall survival (OS), regardless of achieving pCR. This suggests that even if patients do not achieve pCR, they may still benefit from survival gains. A similar outcome was observed in the non-pCR subgroup of the KEYNOTE-522 study. These findings suggest that the focus of immunotherapy in TNBC should not only be on the short-term efficacy endpoint of pCR, but also on long-term survival benefits.
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Oncology Frontier : With many breakthroughs being reported in the TNBC field, what role can ctDNA play in the treatment of early TNBC patients? Please share based on your clinical experience.
Professor Qiang Liu : The concept of ctDNA has been very popular in the last decade, and my research group began focusing on its application in early breast cancer about seven to eight years ago. Our team has explored the clinical value of ctDNA in early breast cancer patients, confirming its utility in monitoring neoadjuvant therapy effectiveness and stratifying recurrence risk. This provides a new method for clinical assessment during the perioperative period of breast cancer, with a related article published in JCO Precision Oncology in 2020. After publication, this article was rated as one of the “Top five most popular articles of 2020” by ASCO, and it was widely shared on Twitter by doctors, nurses, and other medical professionals in the USA. Over the years, the clinical value of ctDNA has become increasingly apparent. Data shows that ctDNA monitoring results can appear 6-12 months earlier than imaging studies such as CT scans, providing a window of opportunity for treatment. Therefore, it helps us identify high-risk patients, reduce the risk of disease recurrence, and offer more personalized treatment strategies, thus preventing some patients from experiencing recurrence and metastasis. Some patients, despite having a relatively high local tumor burden, do not face a high risk of systemic metastasis. Past research indicates that for patients at high local risk, even without systemic treatments, about 40% had a chance of cure, which has increased to over 80% with the advent of chemotherapy, hormone therapy, targeted therapy, and radiation therapy. The key to treating these patients is to determine who should primarily receive local treatment. We are also designing a clinical study to calculate individual recurrence risks through ctDNA levels, avoiding excessive and unnecessary systemic treatments, including chemotherapy, to achieve precise de-escalation therapy. If successful, I believe this will better help patients choose suitable personalized treatment strategies, and this remains our goal for the future.
Professor Qiang Liu
Professor, Chief Physician, Researcher, Doctoral Supervisor
Director of Surgery at Sun Yat-sen Memorial Hospital of Sun Yat-sen University
Executive Deputy Dean of Yi Xian Breast Cancer Hospital, Director of the Breast Cancer Center, Head of the Breast Surgery Department
Member of the ESO-ESMO International Consensus Group for Young Breast Cancer
Standing Committee Member and Deputy Secretary-General of the Breast Cancer Committee of the Chinese Society of Clinical Oncology
Standing Committee Member of the Breast Cancer Committee of the China Anti-Cancer Association
Standing Committee Member of the Tumor Molecular Medicine Committee of the China Anti-Cancer Association
Chairman of the Breast Disease Branch of the Guangdong Medical Association
Vice-Chairman Elect of the Breast Cancer Committee of the Guangdong Anti-Cancer Association
Deputy Editor of the Chinese Journal of General Surgery and Deputy Chief Editor of the Chinese Journal of Endocrine Surgery
PhD in Surgery from the National University of Singapore, former lecturer at Harvard University’s Dana Farber Cancer Center before returning to China
Lead investigator of several major national projects, including key projects funded by the National Natural Science Foundation of China and key international collaboration projects. Pioneer in the application of liquid biopsy and immunotherapy in breast cancer, initiator and framer of China’s first expert consensus on the diagnosis and treatment of young breast cancer, awarded the “National Outstanding Doctor” title by People’s Daily in 2020. Specializes in the diagnosis, surgery, and comprehensive treatment of breast cancer, particularly in high-difficulty breast-conserving surgery, young breast cancer, and personalized precision treatment of triple-negative breast cancer.
