Treatment of breast cancer with low expression of human epidermal growth factor receptor 2 (HER2; HER2-low) has drawn much attention in recent years. With the proven therapeutic effect of trastuzumab deruxtecan (T-DXd) in patients with HER2-low (immunohistochemistry [IHC] 1+, or IHC2+/in situ hybridization [ISH]-) breast cancer, HER2-low may become a new subtype of targeted therapy for breast cancer. The expert committee formulated this consensus based on the current clinical studies and clinical medication experience. The current consensus is the collaborative work of an interdisciplinary working group, including experts in the fields of pathology and oncology. The purpose of this consensus was to guide the clinical diagnosis and treatment of HER2-low breast cancer, thereby prolonging the overall survival of patients.

Background: A vast number of researchers have discovered high levels of human epidermal growth factor receptor-2 (HER2) expression in urothelial carcinoma (UC), but they do not use a uniform scoring system. Based on the 2021 edition of clinical pathological expert consensus on HER-2 testing in UC in China, we investigated the expression level and clinical significance of HER2 in high-grade UC. Furthermore, we looked at the prognosis of patients with locally advanced/metastatic UC after combining HER2 targeting antibody-drug conjugates (ADC) medication disitamab vedotin (DV) with programmed cell death protein 1 (PD-1) inhibitor tislelizumab. Patients and methods: From 2019 to 2022, we collected paraffin specimens of UC from the Department of Urology at the Provincial Hospital Affiliated to Shandong First Medical University. HER2 expression-related factors were investigated. Patients with advanced UC who have failed systemic chemotherapy at least once and had received immune checkpoint inhibitor (ICI) medication during second-line treatment were selected and treated with DV in combination with tislelizumab. We assessed the therapy\'s efficacy and safety. Results: 185 patients with high-grade UC were included in this investigation. 127 patients (68.7%) were HER2 positive (IHC 2+/3+) according to the 2021 Clinical pathological expert consensus on HER2 testing in UC in China. The clinical stage of UC differed statistically significantly between the HER2-and HER2+ groups (p = 0.019). Sixteen advanced UC patients were treated with DV and tislelizumab for a median of 14 months. The disease control rate was 87.5%, while the objective response rate (ORR) was 62.5%. The ORR of HER2+ individuals was higher than that of HER2-individuals (70.0% vs. 50.0%). The median progression-free survival or overall survival was not reached. In this study, the incidence of treatment-related adverse events was 68.8% (11/16), with all of them being grade 1 or 2 adverse reactions. Conclusion: HER2 protein expressed at a high percentage in UC, and 68.7% patients expressed HER2 positive (IHC 2+/3+). HER2+ expression is positively correlated with higher clinical stage of UC. HER2 targeted ADC drug disitamab vedotin combining with PD-1 inhibitor tislelizumab has shown efficacy, safety and controllable adverse reactions in the treatment of advanced UC.

Antibody-drug conjugates (ADCs) are a class of targeted biological agents that link cytotoxic drugs to monoclonal antibodies through linkers. The monoclonal antibody targets tumor cells and transports small-molecule cytotoxic drugs for specific delivery and minimal off-target side effects. September 30, 2022, 14 anti-tumor ADC drugs have been approved for marketing in the world, and four ADCs have been approved in China. With the improvement of the clinical accessibility of ADC drugs, clinicians urgently need to understand the molecular characteristics and mechanisms of ADCs, and clarify the indications for rational use of drugs. Patients\' survival mainly depends on the appropriate dose and course of treatment and also on proper management of adverse reactions. In view of this, on the basis of the \"Expert Consensus on the Clinical Application of Antibody-drug Conjugates for the Treatment of Malignant Tumors (2020 edition)\" , Professional Committee on Clinical Research of Oncology Drugs, Chinese Anti-Cancer Association fully combines the existing clinical research evidence and the feasibility of current ADC drugs in China to update the consensus content. This consensus aims to provide a systematic overview of ADC drugs, so as to provide practical and effective suggestions and references for clinicians to apply and manage ADC drugs more accurately.
抗体药物偶联物(ADC)是一类通过连接子将细胞毒性药物连接到单克隆抗体的靶向生物制剂，可高效靶向转运至目标肿瘤细胞而发挥抗肿瘤作用。截至2022年9月30日，全球已经有14种抗肿瘤ADC药物获得批准上市，中国获得批准上市的ADC有4种。随着ADC药物临床可及性的提高，临床医师亟需深入熟悉其分子特征和机制，明确适应证以合理用药。此外，选择合适的剂量和疗程，有效管理不良反应，可指导临床用药，甚至改善患者的预后转归。鉴于此，中国抗癌协会肿瘤药物临床研究专业委员会在《抗体药物偶联物治疗恶性肿瘤临床应用专家共识(2020版)》的基础上，基于临床研究证据，结合中国目前ADC药物的可及性，对共识进行更新，旨在对ADC药物进行系统性概述，从而为临床医师更精准地应用和管理ADC药物提供切实有效的建议和参考。.

Triple-negative (TN) metastatic breast cancer (mBC) represents the most challenging scenario withing mBC framework, and it has been only slightly affected by the tremendous advancements in terms of drug availability and survival prolongation we have witnessed in the last years for advanced disease. However, although chemotherapy still represents the mainstay of TN mBC management, in the past years, several novel effective agents have been developed and made available in the clinical practice setting. Within this framework, a panel composed of a scientific board of 17 internationally recognized breast oncologists and 42 oncologists working within local spoke centers, addressed 26 high-priority statements, including grey areas, regarding the management of TN mBC. A structured methodology based on a modified Delphi approach to administer the survey and the Nominal Group Technique to capture perceptions and preferences on the management of TN mBC within the Italian Oncology community were adopted. The Panel produced a set of prioritized considerations/consensus statements reflecting the Panel position on diagnostic and staging approach, first-line and second-line treatments of PD-L1-positive/germline BRCA (gBRCA) wild-type, PD-L1-positive/gBRCA mutated, PD-L1-negative/gBRCA wild-type and PD-L1-negative/gBRCA mutated TN mBC. The Panel critically and comprehensively discussed the most relevant and/or unexpected results and put forward possible interpretations for statements not reaching the consensus threshold.

The treatment of breast cancer with low expression of human epidermal growth factor receptor 2 (HER-2) has become a focused area in recent years. With the proved therapeutic effect of antibody-drug conjugate on breast cancer patients with HER-2 low expression, HER-2-low expression may become a new subtype for targeted therapies of breast cancer. Standardized diagnosis and treatment are the foundation to guarantee efficacy. In order to improve the standardization of clinical diagnosis and treatment of HER-2-low breast cancer, the Consensus Expert Committee has summarized the latest domestic and global clinical data and the key relevant publications in recent years. We have combined them with clinical experience of pathologists and oncologists, had a deep discussion within the committee, and developed the consensus. We believe this consensus could help clinicians improve the understanding about HER-2-low breast cancer, promote the accuracy of decision-making and achieve the ultimate goal of prolonging the overall survival and improving the quality of life of patients.
近年来，人表皮生长因子受体2(HER-2)低表达乳腺癌的治疗成为乳腺癌诊疗的热点问题。随着抗体药物偶联物在HER-2低表达乳腺癌患者疗效的确立，HER-2低表达或成为乳腺癌新的靶向治疗亚型。规范诊疗是保证相关疗效的前提，为了更好地规范HER-2低表达乳腺癌临床合理诊疗，中国抗癌协会国际医疗与交流分会和中国医师协会肿瘤医师分会乳腺癌学组参考国内外最新临床研究以及近年来发表的重要参考文献，结合中国病理科医师和肿瘤科医师的临床经验，经专家组讨论后形成HER-2低表达乳腺癌临床诊疗共识，以期加深临床肿瘤医师对HER-2低表达乳腺癌的认识，推进临床决策的精准化，达到延长患者生存时间和提高生活质量的最终目标。.

Human epidermal growth factor receptor 2 (HER2) possesses tyrosine kinase activity and participates in cell growth, differentiation and migration, and survival. Its alterations, mainly including mutations, amplifications, and overexpression are associated with poor prognosis and are one of the major drivers in non-small cell lung cancer (NSCLC). Several clinical trials had been investigating on the treatments of HER2-altered NSCLC, including conventional chemotherapy, programmed death 1 (PD-1) inhibitors, tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs), however, the results were either disappointing or encouraging, but inconsistent. Trastuzumab deruxtecan (T-DXd) was recently approved by the Food and Drug Administration as the first targeted agent for treating HER2-mutant NSCLC. Effective screening of patients is the key to the clinical application of HER2-targeted agents such as TKIs and ADCs. Various testing methods are nowadays available, including polymerase chain reaction (PCR), next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), etc. Each method has its pros and cons and should be reasonably assigned to appropriate patients for diagnosis and guiding treatment decisions. To help standardize the clinical workflow, our expert group reached a consensus on the clinical management of HER2-altered NSCLC, focusing on the diagnosis and treatment strategies.

As a newly emerged class of anticancer bioagents in the most precise and selectively targeted way, antibody-drug conjugate (ADC) combines the cancer-targeting abilities of monoclonal antibodies with the cytotoxicity potency of payload, delivering highly cytotoxic drug into tumors via \'targeted chemotherapy\'. ADC has revolutionized the treatment landscape of human epidermal growth factor receptor 2 positive and triple negative subtypes in breast cancer. Three ADCs have been approved by U. S. Food and Drug Administration with breast cancer indications, including trastuzumab emtansine (T-DM1; also approved in China), trastuzumab deruxtecan (T-DXd, DS-8201) and sacituzumab govitecan (IMMU-132; also approved in China). Antibodies, cytotoxic drug, linker, and conjugation process are implicated in ADC profile, resulting in unique adverse drug reactions and toxicity heterogeneity within ADC class. For example, more attention should be paid to the management of thrombocytopenia, hepatotoxicity, and reductions in left ventricular ejection fraction (LVEF) in patients treated with trastuzumab emtansine; clinical physicians should pay attention to the risk of neutropenia, interstitial lung disease/pneumonitis, and reductions in LVEF when treated with trastuzumab deruxtecan; sacituzumab govitecan most frequently caused neutropenia, anemia and diarrhea requiring close monitor. ADC has generally favorable safety profiles, and dose modifications and/or symptomatic supporting treatment are effective in terms of toxicity management. This consensus aims at providing guidance for clinical oncologists of early detection, regular assessment, timely management and follow-up monitor of ADC-associated adverse reactions/events.
抗体药物偶联物(ADC)将单克隆抗体的选择性与有效载荷的细胞杀伤特性合二为一，通过靶向化疗的方式将细胞毒性药物释放至肿瘤，是一类相对新颖的具有高度靶向性的抗癌生物制剂。在乳腺癌领域中，ADC改变了人类表皮生长因子受体2阳性以及三阴性乳腺癌的治疗格局。目前获得美国食品药品监督管理局批准的3种ADC有乳腺癌适应证，分别为恩美曲妥珠单抗、Trastuzumab deruxtecan和戈沙妥珠单抗，其中恩美曲妥珠单抗和戈沙妥珠单抗也在中国获得批准上市。鉴于ADC涉及抗体、细胞毒性制剂、连接子以及偶联过程，因此导致了ADC不良反应的独特性及其类别内安全谱的异质性。接受恩美曲妥珠单抗治疗的患者需特别关注血小板减少、肝不良反应以及左心室射血分数(LVEF)降低；Trastuzumab deruxtecan治疗期间应关注中性粒细胞减少、间质性肺疾病或非感染性肺炎以及LVEF降低的风险；戈沙妥珠单抗治疗常导致中性粒细胞减少、贫血，同时需密切监测腹泻。ADC总体上安全性良好，剂量调整和(或)对症支持治疗为有效的管理方式。中国医师协会肿瘤医师分会乳腺癌学组和中国抗癌协会国际医疗交流分会组织专家共同制定了中国乳腺癌抗体药物偶联物安全性管理专家共识，旨在为临床肿瘤医师提供ADC相关不良反应或不良事件的早期识别、定期评估、及时管理以及随访监测的实践指导。.

Antibody-drug conjugate (ADC) is a type of targeted biological agent which connect cytotoxic drug to monoclonal antibody by a connector head, which enables monoclonal antibody acted as a carrier to efficiently transport small molecular cytotoxic drugs to target tumor cells. It is very important for clinicians to have an in-depth understanding of the molecular characteristics and mechanism of ADC drugs, rationally choose the appropriate dose, course of treatment and manage adverse reactions according to the indications during the clinical application of ADC drugs, which may even affect the survival of patients. Therefore, the consensus aims to conduct a systematic overview of commercially available ADC drugs, provide effective recommendations and references for clinicians to better apply and manage ADC drugs.
抗体药物偶联物(ADC)是一类通过连接头将细胞毒性药物连接到单克隆抗体的靶向生物药剂，以单抗作为载体将小分子细胞毒性药物以靶向方式高效地运输至目标肿瘤细胞中。深入了解ADC药物的分子特征和机制特点，并在ADC药物临床应用过程中根据适应证合理用药，选择合适的剂量和疗程，有效管理不良反应，对临床医师而言十分重要，甚至可能影响患者的生存转归。因此，共识旨在对市面可及的ADC药物进行系统概述，从而为临床医师更好地应用和管理ADC药物提供切实有效的建议和参考。.