Editor's Note: From August 2 to 4, 2024, the 7th Oncology Precision Diagnosis and Treatment and the 10th Breast Cancer Individualized Treatment Conference (COMB), hosted by the China Cancer Foundation and the Beijing Breast Disease Prevention and Treatment Society, took place in Beijing. This conference focused on the development of individualized precision treatment in the field of breast cancer in China. Dr. Jin Zhang from Tianjin Medical University Cancer Institute and Hospital chaired a session titled “New Concepts in Regional Management of Breast Cancer,” discussing the precise development of comprehensive regional treatment for breast cancer. At the conference, Oncology Frontier had the opportunity to interview Dr. Jin Zhang, who shared insights on the de-escalation in early breast cancer surgery and explored the current status of anti-HER2 therapy and its clinical practice in advanced breast cancer.

Oncology Frontier: Could you tell us about the current status of treatment for HER2-positive advanced breast cancer?

Dr. Jin Zhang: The treatment for HER2-positive breast cancer has seen breakthrough advancements. At the American Society of Clinical Oncology (ASCO) annual meeting in June, studies highlighted the differential efficacy of anti-HER2 therapies based on varying HER2 expression levels, offering strong support for clinical practice improvements in treating HER2-positive advanced breast cancer. These developments have deepened our understanding of anti-HER2 therapy, allowing us to tailor individualized treatment options based on specific HER2 expression levels, ultimately leading to better survival outcomes for patients with advanced HER2-positive breast cancer.

Oncology Frontier: Antibody-drug conjugates (ADCs) have significantly prolonged survival for HER2-positive advanced breast cancer patients, changing the current treatment landscape. Could you share the future prospects of ADCs in this setting?

Dr. Jin Zhang: Clinical research on ADCs has already extended across all four subtypes of breast cancer, with data available for each. However, in clinical practice, ADCs have mainly been approved and applied for HER2-positive and triple-negative breast cancer. In China, the HER2-targeted ADCs that are currently approved for clinical use, starting with T-DM1 and now T-DXd, have achieved even better efficacy.

As our understanding of the biological behavior and molecular nature of HER2 expression deepens, we have found that T-DXd exhibits varying degrees of efficacy across different HER2 expression levels. For HER2-positive breast cancer, T-DXd’s efficacy is excellent. For those with low HER2 expression, T-DXd shows stratified efficacy based on HER2 levels, leading to improved overall survival benefits for patients. These effects have had a profound impact on treatment. In the future, we must continue refining our stratification of target populations for T-DXd and optimizing combination therapy strategies to improve outcomes.

Oncology Frontier: What unmet clinical needs do you see in the treatment of HER2-positive advanced breast cancer, and how can clinicians improve precision treatment in this area?

Dr. Jin Zhang: In clinical practice, the standards for identifying HER2-positive patients are well-established. However, for those with low HER2 expression, it’s still unclear whether different levels of expression represent distinct subgroups. This requires closer collaboration between pathologists and clinicians. In metastatic breast cancer, there is often spatiotemporal heterogeneity between primary tumors and metastases. A patient’s HER2 status may differ between the primary tumor and metastases, necessitating re-testing of HER2 at the time of metastasis. However, not all metastatic lesions can undergo pathological evaluation. This raises a critical issue: how to guide treatment decisions based on previous HER2 test results from primary tumors and lymph nodes when pathological evidence for metastases is lacking. A clear pathway needs to be established between pathologists and clinicians for making these determinations. With the development of more effective therapies, applying them precisely to the right patient populations is key. In the era of precision medicine, we must fully understand the molecular nature of tumors, tumor heterogeneity, and drug mechanisms to translate these insights into clinical practice and guide treatment strategies.

Oncology Frontier: You chaired the session on “New Concepts in Regional Management of Breast Cancer” at this year’s COMB conference. In recent years, surgical approaches in breast cancer treatment have also made significant progress. Could you review the key advances in breast cancer surgery and discuss how to further enhance precision surgery?

Dr. Jin Zhang: As early diagnosis and systemic treatment have improved, the local treatment of breast cancer has evolved into a more comprehensive approach. Surgery, being inherently destructive, should aim to enhance treatment outcomes and improve the patient’s quality of life by exploring de-escalation strategies that avoid unnecessary surgeries or radiotherapy. The development and application of de-escalation approaches are often based on a deeper understanding of the molecular nature and metastatic behavior of tumors. Surgical treatment for breast cancer has progressed from radical mastectomy to breast-conserving surgery, driven by advances in the understanding of breast cancer biology. This shift reflects the evolution from the Halsted model to the Fisher model of cancer treatment. The future will undoubtedly focus on implementing precision medicine, which is inseparably tied to advancements in imaging and pathology. If we can clearly understand the molecular mechanisms behind breast cancer and apply this knowledge to guide de-escalation strategies, reducing the risk of local recurrence, then de-escalation treatments will be bold and feasible in clinical practice. The key challenge remains finding ways to de-escalate local treatment while minimizing recurrence risk.

Dr. Jin Zhang:

• Title: Professor, Chief Physician, Doctoral Supervisor
• Positions: Assistant Director, Tianjin Medical University Cancer Institute and Hospital Executive Deputy Director, Tianjin Breast Cancer Prevention and Treatment Research Center Chief, Breast Oncology Department III, Tianjin Medical University Cancer Institute and Hospital
• Honors: Expert with Special Government Allowance from the State Council of China Awarded the title of “Famous Doctor of the Nation” (4th Edition) Member of the ESMO Breast Cancer Expert Committee Chairperson of the 10th Chinese Anti-Cancer Association Breast Cancer Professional Committee Vice-Chairperson of the Multidisciplinary Tumor Diagnosis and Treatment Committee of the Chinese Anti-Cancer Association Member of the Oncology Committee of the Chinese Medical Association Vice-Chair of the Early Diagnosis and Treatment of Malignant Tumors Task Force of the Oncology Committee, Chinese Medical Association Member of the Breast Cancer Working Group, Surgery Branch of the Chinese Medical Association Vice-Chairperson of the Breast Surgery Expert Group, Surgery Branch of the Chinese Medical Doctor Association Standing Member of the Multidisciplinary Tumor Diagnosis and Treatment Expert Committee of the Chinese Medical Doctor Association Chairperson of the Oncology Committee, Tianjin Medical Association Executive Director of the Tianjin Anti-Cancer Association Chairperson of the Breast Cancer Quality Control Expert Committee, Tianjin