Editor's Note: During the recent 2024 Straits Breast Cancer Forum and Fujian Medical Association Breast Disease Division Meeting, Oncology Frontier had the privilege of inviting Dr. Jian Huang from The Second Affiliated Hospital of Zhejiang University School of Medicine. He shared in-depth insights into advancements in neoadjuvant therapy for breast cancer downstaging and breast conservation, the significance and challenges of functional minimally invasive surgery, and his team's exploration and achievements in the field of basic and translational breast cancer research.

Progress in Neoadjuvant Therapy for Breast Cancer Downstaging and Breast Conservation

Oncology Frontier: What progress has been made in recent years in the use of neoadjuvant therapy for breast cancer downstaging and breast conservation?

Dr. Jian Huang: Neoadjuvant therapy has proven to be a vital approach in the treatment of locally advanced breast cancer, particularly in improving breast-conserving and axillary preservation rates. In recent years, we have made significant strides in techniques, drugs, and treatment concepts.

Our primary goal is to preserve the breast and axillary lymph nodes as much as possible. Neoadjuvant chemotherapy plays a crucial role in achieving this but must be complemented by other techniques. For example, our center, along with other institutions, has been utilizing clip-marking technology to mark tumors and metastatic lymph nodes, combined with surface markers for dynamic tracking.

We also integrate molecular functional imaging with traditional modalities such as ultrasound, mammography, and MRI, allowing for a more precise assessment of responses to neoadjuvant therapy and accurate tumor localization. These advancements enable us to achieve precise, curative, and functional breast and axillary surgeries, ensuring optimal treatment outcomes.

The Role and Challenges of Functional Minimally Invasive Surgery

Oncology Frontier: With increasing emphasis on aesthetics, what is the significance of functional minimally invasive surgery in this context? What challenges does it present?

Dr. Jian Huang: Today, surgeons must not only complete surgeries but also address post-operative symptoms, physiological changes, psychological well-being, and social functionality. Comprehensive, continuous management is essential.

Breast and axillary preservation are vital components of functional breast surgery, but the scope extends further. We must enhance patients’ quality of life, boost their confidence, and address their physical and psychological needs alongside prolonging survival.

Achieving these outcomes requires advancements in surgical techniques, psychological support, and leveraging advanced technologies. For instance, we need to determine lymph node metastasis accurately, identify sentinel lymph nodes, and suture lymphatic vessels to reduce lymphedema.

In breast cancer surgery, precise judgment of surgical margins and extent is critical. Advanced technologies such as 3D printing and three-dimensional imaging enable a comprehensive understanding of the tumor’s three-dimensional structure and boundaries. This allows for minimal removal of normal tissue while meeting curative requirements.

AI also plays an important role by integrating imaging data, clinical evaluations, and patient-reported outcomes, helping us assess treatment efficacy and post-surgical functionality.

Functional minimally invasive surgery requires collaboration across multiple disciplines and fields, marking the future trajectory of advancements in functional breast cancer surgery.

Exploration and Advances in Basic and Translational Research in Breast Cancer

Oncology Frontier: Your team has conducted significant research in the field of basic and translational breast cancer studies. What recent progress has been made, and how can these findings be translated into clinical practice to benefit patients?

Dr. Jian Huang: As surgeons, we aim to not only provide optimal clinical care but also to address clinical challenges and patient needs by transforming them into research questions. This integration of clinical and research teams allows us to approach breast cancer treatment holistically.

For example, improving the pathological complete response (pCR) rate during neoadjuvant therapy remains a critical focus. While standard treatment protocols achieve a pCR rate of approximately 70%, 30% of patients still do not respond fully. Precision diagnostics and individualized drug selection are essential to enhance these outcomes.

To address this, we have developed a high-fidelity in vitro tumor microenvironment model, which includes tumor organoids and micro-tissue culture systems, combined with in vivo molecular functional imaging techniques. These models enable early efficacy assessment and response prediction, leading to increased pCR rates and a reduction in axillary dissection rates. Currently, our breast center has achieved a breast conservation rate of 60% and a 50% reduction in axillary dissection rates, greatly enhancing the implementation of functional breast surgery.

Additionally, our research delves into the tumor microenvironment, particularly the immune microenvironment. We have found that γδT cells are positively correlated with the efficacy of neoadjuvant therapy. For example, higher levels of NK-like cells predict better therapeutic responses, while elevated levels of CD73- or CD39-positive γδT cells are associated with poorer outcomes. These insights into immune cell behavior provide valuable predictive markers for therapy efficacy.

Our collaboration with multidisciplinary teams at Zhejiang University further supports our efforts. We employ advanced technologies, such as organ-on-chip systems and microfluidic platforms, to rapidly assess drug sensitivity using minimal tissue samples. This initiative has led to the establishment of a comprehensive system that includes patient cohorts, a tumor organoid biobank, and clinical efficacy evaluation techniques.

The greatest strength of our team lies in integrating these innovative approaches into a unified platform, which has become a hallmark of our research. By combining clinical indicators, immune markers, and in vitro drug sensitivity predictions, we aim to elevate our overall predictive capabilities and deliver more personalized and effective treatments to patients.

Dr. Jian Huang

• Doctor of Oncology, Professor, Doctoral Supervisor
• Executive Vice President, Second Affiliated Hospital, Zhejiang University School of Medicine
• Head of Breast Surgery
• Specially Appointed Qiu Shi Physician, Zhejiang University
• Recipient of the State Council Special Allowance and recognized as an outstanding mid-career expert in Zhejiang Province
• Member of the Expert Panel for the Chinese Breast Cancer Screening and Early Diagnosis and Treatment Guidelines
• Standing Member of the Breast Cancer Professional Committee, Chinese Anti-Cancer Association, and former Chair of the Breast Cancer Professional Committee, Zhejiang Anti-Cancer Association
• Director of the Zhejiang Provincial Breast Cancer Screening Training and Quality Control Center
• Standing Member of the Breast Cancer Committee, Chinese Society of Clinical Oncology (CSCO)
• Member of the Breast Surgery Group, Chinese Society of Surgery
• Chair and Standing Member of the Zhejiang Branch, Chinese Society of Evidence-Based Medicine
• Director of the Zhejiang Provincial Key Laboratory of Tumor Microenvironment and Immunotherapy
• Director of the Zhejiang Provincial International Collaborative Innovation Base for Tumor Immunotherapy Diagnostics and New Technology