Editor's Note: The Breast Cancer Committee of the Chinese Society of Clinical Oncology (CSCO BC) has developed the CSCO Breast Cancer Diagnosis and Treatment Guidelines (hereafter referred to as the CSCO BC Guidelines), which have become a crucial reference for Chinese clinicians, serving as a "navigation tool" for clinical decision-making. With the rapid progress of clinical oncology, especially the continuous emergence of original Chinese research and treatment strategies, the CSCO BC Guidelines have not only stayed at the forefront of international developments but have also incorporated more "Chinese characteristics." This has attracted increasing attention from international experts. Recently, the English version of the CSCO BC Guidelines was published in the Translational Breast Cancer Research (TBCR), further showcasing China's experience and wisdom in breast cancer management to the global oncology community. Oncology Frontier invited Dr. Zefei Jiang, Dr. Chunfang Hao, Dr. Xu Liang, Dr. Jin Yang, Dr. Min Yan, and Dr. Yueping Liu to provide an overview of the key updates to the CSCO BC Guidelines and share their insights with international peers through this global platform.

• Dr. Zefei Jiang
• CSCO BC Guidelines Lead China’s Approach to the World

As clinicians, we constantly seek reliable, high-quality guidelines to guide our clinical practice. The Chinese Society of Clinical Oncology (CSCO) is keenly aware of this responsibility and is committed to integrating the latest international developments with China’s specific practices and drug accessibility to continuously optimize its breast cancer treatment recommendations. Since 2017, we have categorized treatment strategies into “basic” and “optional” to ensure adherence to fundamental treatment pathways while offering patients optimized treatment choices. In recent years, we have further refined the guidelines into a three-tier recommendation system. Tier 1 focuses on therapies with stable therapeutic value and broad accessibility; Tier 2 incorporates newer therapies that may not yet be fully adopted or covered by insurance but provide patients with more advanced treatment options; Tier 3 includes therapies that require further evaluation or are relatively outdated, which are not recommended as first-line options.

We are honored that the full English version of the CSCO BC Guidelines has been published in TBCR, allowing international colleagues to appreciate the contributions of Chinese clinical oncologists. Experts from Europe, the US, Japan, and other countries have provided highly positive feedback in TBCR, particularly praising our dedicated chapter on immunotherapy, which explores strategies for neoadjuvant immunotherapy in early-stage disease and immunotherapy in advanced relapsed cases. International peers have also recognized China’s innovative treatment strategies, such as small-molecule TKIs for HER2-positive breast cancer, which were developed through multicenter studies led by Academician Binghe Xu and myself and have been published in international journals.

With increasing global engagement, some international experts have realized that they face similar challenges regarding treatment accessibility or are in situations comparable to those in China. This has led to growing interest in the CSCO BC Guidelines. We are deeply grateful to our expert group members, international colleagues, and media partners for their support and promotion of the guidelines. CSCO BC will continue to uphold global standards while incorporating Chinese characteristics, striving to provide better treatment options and help achieve more curative outcomes for patients in China and abroad.

• Dr. Chunfang Hao
• Overview of HER2-Positive Breast Cancer in the CSCO BC Guidelines

The latest version of the CSCO BC Guidelines addresses four main areas in the treatment of HER2-positive breast cancer: neoadjuvant therapy, post-neoadjuvant adjuvant therapy, standard adjuvant therapy, and treatment for advanced HER2-positive breast cancer.

In neoadjuvant therapy, in addition to recommending the HP dual-target regimen, the guidelines also recommend the “large and small molecule” dual-target regimen (PyHT), based on the PHEDRA study. For patients achieving a pathological complete response (pCR) after neoadjuvant therapy, HP maintenance is still recommended, while non-pCR patients are advised to receive intensified treatment with T-DM1. For patients who cannot tolerate T-DM1 (e.g., due to thrombocytopenia), alternative intensified targeted therapies are available. Standard adjuvant therapy remains largely unchanged, with a focus on high-risk patients who may benefit from dual-target or sequential treatment. As more evidence accumulates, we tend to prefer neoadjuvant therapy for T2 or larger HER2-positive early breast cancer, with adjuvant therapy decisions based on the response to neoadjuvant treatment.

For advanced disease, there are several highlights. In first-line treatment, in addition to the HP dual-target regimen, the “large and small molecule” dual-target regimen (PyHT) is recommended, based on the PHILA study. For second-line treatment, T-DXd has now surpassed T-DM1 in recommendation levels. The small-molecule TKI pyrotinib, supported by two phase 3 clinical trials, has also been included in the national insurance list for 2024.

It is important to note that the CSCO BC Guidelines comprehensively consider evidence-based medical research, drug accessibility, and patient tolerance when recommending treatment strategies, aiming to provide patients with staged, stratified, and optimized treatment plans while emphasizing the importance of comprehensive management.

• Dr. Xu Liang
• Overview of HR-Positive Breast Cancer in the CSCO BC Guidelines

The CSCO BC Guidelines have become an essential reference tool for Chinese clinicians. Compared to the 2023 and earlier editions, the 2024 guidelines have introduced several adjustments in the treatment recommendations for HR-positive breast cancer. For early-stage disease, CDK4/6 inhibitors combined with aromatase inhibitors are now recommended for neoadjuvant and adjuvant therapy. Currently, abemaciclib has been approved for widespread use in patients with ≥4 positive lymph nodes or 1-3 positive nodes with high-risk factors. For patients with poor tolerance, the ribociclib regimen, based on the NATALEE study, is also an option, reflecting the forward-looking nature of the CSCO BC Guidelines.

A significant change in advanced disease treatment is the unified recommendation level for all CDK4/6 inhibitors, as numerous clinical trials have demonstrated consistent survival benefits. With several CDK4/6 inhibitors now covered by national insurance, accessibility has greatly improved. In second-line treatment, the AKT inhibitor capivasertib, supported by the CAPItello-291 study, is the first phase 3 trial to show positive results for CDK4/6-resistant populations, and the CSCO BC Guidelines have included it as a third-tier recommendation for patients with PAM pathway mutations.

In addition, the 2024 guidelines introduce a new chapter on HER2-low expression. Based on the remarkable efficacy of DS-8201 (T-DXd) in the DB-06 and DB-04 clinical trials, DS-8201 is recommended for HER2-low patients who are resistant to CDK4/6 inhibitors and have undergone chemotherapy. The TROP-2 ADC sacituzumab govitecan is also listed as an option for later-line treatment. These updates highlight the guidelines’ commitment to staying at the forefront of clinical practice.

• Dr. Jin Yang
• Overview of Triple-Negative Breast Cancer in the CSCO BC Guidelines

The CSCO BC Guidelines are known for their authority, innovation, and practical applicability, tailored to China’s specific circumstances. The 2024 guidelines introduce a dedicated section on immunotherapy for triple-negative breast cancer (TNBC), which has gained significant attention.

For early-stage TNBC, the guidelines emphasize the importance of neoadjuvant chemotherapy combined with immunotherapy, recognizing this as the key pathway to achieving the best chance of cure. For patients eligible for neoadjuvant therapy, the TP sequential AC regimen from the KEYNOTE-522 study or the TP combined immunotherapy regimen from the cTRIO study is recommended. To ensure the best treatment outcome, the guidelines stress the completion of the full course of neoadjuvant chemotherapy combined with immunotherapy before surgery.

In advanced TNBC, based on data from the KEYNOTE-355 and TORCHLIGHT studies, chemotherapy combined with immunotherapy is recommended as the first-line treatment of choice for PD-L1-positive patients. It’s worth noting that these two studies used different PD-L1 cutoffs—KEYNOTE-355 focused on patients with PD-L1 >10, while TORCHLIGHT, led by Chinese scholars, used a CPS score of ≥1, providing more locally relevant guidance for Chinese patients.

Additionally, the TROP-2-targeting ADC sacituzumab govitecan is now included in the guidelines as a treatment option for advanced TNBC, offering more diverse choices for patients. The guidelines also feature a chapter on HER2-low expression, recommending DS-8201 as a second-line or later treatment option for HER2-low TNBC patients.

• Dr. Min Yan
• Overview of Breast Cancer with Brain Metastases in the CSCO BC Guidelines

The CSCO BC Guidelines have included a dedicated chapter on brain metastases, highlighting their unique clinical significance and treatment challenges. Breast cancer is second only to lung cancer in terms of brain metastasis rates, with HER2-positive and triple-negative breast cancers being more prone to brain metastases. Enhanced MRI is recommended as the preferred diagnostic tool for detecting small lesions and meningeal metastases.

In terms of treatment, the CSCO BC Guidelines deviate from the traditional approach of primarily using local therapies for brain metastases and instead emphasize the transformative role of new systemic therapies that penetrate the blood-brain barrier. Both small-molecule TKIs and large-molecule ADCs have demonstrated promising results in the treatment of brain metastases, with good central nervous system activity. The guidelines recommend prioritizing systemic treatment with brain-penetrating drugs for HER2-positive patients who do not require immediate local intervention.

This approach is supported by evidence from key studies. For example, the PERMEATE trial reported a 74.6% objective response rate for pyrotinib combined with capecitabine in treating active brain metastases. The DB-01, DB-02, DB-03 studies with DS-8201 and the TUXEDO-1 trial also demonstrated the efficacy of DS-8201 in brain metastases.

International guidelines, such as those from the NCCN, also recommend small-molecule TKIs like tucatinib for treating brain metastases, even though these drugs are not yet widely available in China. Nonetheless, their emergence offers new hope for breast cancer patients with brain metastases, and we look forward to the introduction of more innovative drugs in the future to extend survival and improve quality of life for these patients.

• Dr. Yueping Liu
• Overview of Breast Cancer Pathology Diagnosis in the CSCO BC Guidelines

As precision medicine advances, the requirements for pathology diagnosis have become more demanding, playing a crucial role in the success of targeted therapies. The rise of antibody-drug conjugates (ADCs), especially for patients with low or ultra-low HER2 expression, has made accurate detection even more essential. Pathology departments must now work to accurately identify patients with low or ultra-low HER2 expression to ensure they receive the most appropriate targeted treatment. The CSCO BC Guidelines have been revised accordingly, which means that clinical pathology testing requirements have changed. More precise identification of HER2-low and ultra-low patients has become a new focus for pathology testing.

With the deepening research on molecular subtypes of breast cancer, mutations in key signaling pathways like the PAM (PI3K-AKT-mTOR) pathway and HDR (homologous recombination repair) pathway have become new treatment targets. Targeted therapies aimed at these pathways require precise genetic testing to identify patients with specific mutations. However, genetic testing technologies have not yet been fully standardized in China, presenting challenges for consistency and accuracy in clinical diagnosis. Therefore, establishing and promoting unified genetic testing standards and procedures to enhance the accuracy and reproducibility of testing is critical for advancing precision medicine in breast cancer treatment.

Against this backdrop, the sensitivity, specificity, and standardization of pathology testing directly impact the effectiveness of precision treatments. Establishing and promoting standardized testing procedures will be a key priority moving forward. The CSCO BC Guidelines incorporate both domestic and international evidence-based medical research to address the key issues in breast cancer pathology. These recommendations not only draw on international experience but also take into account the varying testing conditions across different regions and hospitals in China, making them highly adaptable. In the future, further improving standard operating procedures (SOPs) for pathology testing and ensuring quality control will be essential, particularly as demand for precision treatments continues to grow.

Dr. Zefei Jiang Vice Director, Cancer Medicine Department, The Fifth Medical Center of Chinese PLA General Hospital Chairman, Breast Disease Committee, Beijing Medical Association Vice President and Secretary-General, Chinese Society of Clinical Oncology (CSCO) Member, St. Gallen International Breast Cancer Consensus Panel

Dr.  Chunfang Hao Tianjin Cancer Hospital Airport Hospital

MD, PhD, Master’s Supervisor

Director of the Breast Medical Oncology Department, Tianjin Cancer Hospital Airport Hospital

Member of the Breast Cancer Expert Committee, Chinese Society of Clinical Oncology (CSCO)

Member of the Breast Cancer Professional Committee, Chinese Anti-Cancer Association

Member of the Oncology Clinical Chemotherapy Professional Committee, Chinese Anti-Cancer Association

Member of the Oncology Prevention and Treatment Science Popularization Professional Committee, Chinese Anti-Cancer Association

Executive Member of the Breast Professional Committee, Chinese Medical Women’s Association

Vice Director of the Breast Cancer Youth Committee, Beijing Cancer Prevention and Treatment Society

Executive Member of the Breast Cancer Personalized Diagnosis and Treatment and MDT Professional Committee, Beijing Cancer Prevention and Treatment Society

Dr. Xu Liang Peking University Cancer Hospital

MD, Breast Medical Oncology Department, Peking University Cancer Hospital, Deputy Chief Physician

Executive Committee Member of the Breast Professional Committee, Chinese Medical Women’s Association

Member of the Breast Disease Branch, Beijing Medical Association

Member of the Internal Medicine Professional Committee, Beijing Breast Disease Prevention and Treatment Society

Executive Committee Member of the Oncology Immunotherapy Professional Committee, Beijing Breast Disease Prevention and Treatment Society

Graduated from the Clinical Medicine major at Peking University People’s Hospital in 2005, and has been working in the Breast Medical Oncology Department of Peking University Clinical Oncology College since graduation, specializing in the diagnosis and treatment of advanced breast cancer. He has also studied at the Tokyo Cancer Center in Japan and the Curie Institute in France, conducting translational medical research related to breast cancer. The main research direction and focus of work are standardized and personalized treatment for advanced breast cancer. As a key collaborator, he has completed more than ten international and domestic multicenter clinical studies on advanced breast cancer, and has published more than ten papers in core journals and journals indexed by SCI.

Dr. Jin Yang Xi’an Jiaotong University First Affiliated Hospital

Director of the Cancer Center and Director of the Precision Research Center, Xi’an Jiaotong University First Affiliated Hospital

MD, Chief Physician/Professor, PhD Supervisor, Deputy Director of the Department of Oncology

Executive Committee Member of the Breast Cancer Professional Committee, Chinese Research Hospital Association

Member of the Breast Cancer Professional Committee, National Cancer Quality Control Center

Member of the Breast Cancer Professional Committee, Chinese Society of Clinical Oncology (CSCO)

Member of the Breast Cancer Professional Committee, Chinese Anti-Cancer Association

Executive Committee Member of the Clinical Oncology Committee, Chinese Medical Women’s Association

Member of the Breast Cancer Professional Committee, Chinese Medical Doctor Association Oncology Branch

Deputy Director of the Breast Oncology Group, Tumor Marker Professional Committee, Chinese Anti-Cancer Association

Deputy Head of the Breast Oncology Group, Precision Medicine and Oncology MDT Professional Committee, Chinese Research Hospital Association

Member of the Tumor Integrated Cardiology Professional Committee, Chinese Anti-Cancer Association

Executive Committee Member of the Oncology Internal Medicine Branch, Shaanxi Medical Association

Director of the Anticancer Pharmacology Professional Committee, Shaanxi Anti-Cancer Association

Director of the Oncology Precision Treatment Professional Committee, Xi’an Cancer Rehabilitation Association

Visiting Scholar at the Marlene and Stewart Greenbaum Cancer Center, University of Maryland, USA

May 1st Female Model of Shaanxi Province

Published more than 50 papers, with 47 indexed by SCI

Principal investigator of 4 general projects of the National Natural Science Foundation of China

Won 2 Shaanxi Provincial Science and Technology Progress Awards, 2 University Science and Technology Progress Awards

Dr. Min Yan

Henan Province Cancer Hospital

Breast Surgery Department of Henan Province Cancer Hospital, Deputy Director of Henan Province Breast Disease Diagnosis and Treatment Center

Chief Physician, MD, PhD

Executive Committee Member of the Breast Cancer Expert Committee, Chinese Society of Clinical Oncology (CSCO)

Executive Committee Member of the Breast Disease Research Center Professional Committee, Chinese Medical Women’s Association

Executive Committee Member of the Breast Cancer Study Group, Chinese Medical Doctor Association Oncology Branch

Executive Committee Member of the Tumor Metastasis Professional Committee, China Medical Education Association

Member of the Multi-primary and Unknown Primary Tumor Expert Committee, Chinese Anti-Cancer Association

Member of the Oncology Expert Committee, National Health Commission Capacity Building and Continuing Education

Deputy Director of the Breast Oncology Group, Precision Medicine and Oncology MDT Professional Committee, Chinese Research Hospital Association

Deputy Director of the Breast Cancer Expert Committee, Henan Province Cancer Diagnosis and Treatment Quality Control Center

Deputy Director of the Breast Professional Committee, Henan Life Care Association

Deputy Director of the Breast Disease Management and Innovation Branch, Henan Province Hospital Association

Visiting Scholar at the Marlene and Stewart Greenbaum Cancer Center, University of Maryland, USA

May 1st Women’s Model of Henan Province

Published more than 50 papers, with 47 indexed by SCI

Principal investigator of 4 general projects of the National Natural Science Foundation of China

Won 2 Henan Provincial Science and Technology Progress Awards, 2 University Science and Technology Progress Awards

Dr. Yueping Liu Hebei Medical University Fourth Hospital / Hebei Cancer Hospital

Pathology Department Director, Hebei Medical University Fourth Hospital / Hebei Cancer Hospital

Chief Physician / Professor, MD, PhD, PhD Supervisor

Selected for the first level of Hebei Province’s “333 Talent Project”, enjoys special government allowances from the Hebei Provincial Government

Member of the Pathology Branch of the Chinese Medical Association

Group Leader of Breast Tumor, Oncology Pathology Committee, Chinese Anti-Cancer Association Vice Chairman of the Oncology Pathology Expert Committee, Chinese Society of Clinical Oncology (CSCO)

Vice Chairman of the Gastrointestinal Polyps and Precancerous Lesions Committee, Chinese Anti-Cancer Association

Director of the Pathology Branch of the Hebei Medical Association

Director of the Pathology Physicians Branch of the Hebei Physicians Association

Deputy Editor-in-Chief of “Clinical and Experimental Pathology”