人表皮生长因子受体 2 (HER2) 表达是乳腺癌 (BC) 的重要生物标志物。大多数被归类为 HER2 阴性 (HER2-) 的 BC 病例表达低水平的 HER2 [免疫组织化学 (IHC) 1 或 IHC 2 /原位杂交未扩增 (ISH-)]，并且代表临床相关的治疗类别，适合靶向治疗使用最近批准的针对 HER2 的抗体药物偶联物进行治疗。一组具有乳腺病理学和 BC 生物标志物测试专业知识的执业病理学家，概述了在 HER2 IHC 评分 BC 方面达成共识的最佳实践和指南。作者描述了 IHC 测试和 HER2 低表达 BC 评分的当前知识和挑战。为准确识别表达低水平 HER2 的 BC 提供最佳实践和指导。这些专家病理学家提出了一种通过经过验证的 IHC 检测来评估 HER2 表达的算法，并纳入了 2023 年美国临床肿瘤学会和美国病理学家学会指南更新。作者还就何时寻求 HER2 IHC 评分共识、如何将 HER2-low 纳入 IHC 报告以及提供 HER2 IHC 染色示例（包括具有挑战性的病例）提供指导。对 HER 蛋白过表达/基因扩增阴性的 BC 病例的认识以及靶向治疗的相关临床相关性凸显了准确的 HER2 IHC 评分对于最佳治疗选择的重要性。© 2024 作者。组织病理学由约翰·威利出版

Human epidermal growth factor receptor 2 (HER2) expression is an important biomarker in breast cancer (BC). Most BC cases categorised as HER2-negative (HER2-) express low levels of HER2 [immunohistochemistry (IHC) 1+ or IHC 2+/in-situ hybridisation not amplified (ISH-)] and represent a clinically relevant therapeutic category that is amenable to targeted therapy using a recently approved HER2-directed antibody-drug conjugate. A group of practising pathologists, with expertise in breast pathology and BC biomarker testing, outline best practices and guidance for achieving consensus in HER2 IHC scoring for BC.The authors describe current knowledge and challenges of IHC testing and scoring of HER2-low expressing BC and provide best practices and guidance for accurate identification of BCs expressing low levels of HER2. These expert pathologists propose an algorithm for assessing HER2 expression with validated IHC assays and incorporate the 2023 American Society of Clinical Oncology and College of American Pathologist guideline update. The authors also provide guidance on when to seek consensus for HER2 IHC scoring, how to incorporate HER2-low into IHC reporting and present examples of HER2 IHC staining, including challenging cases.Awareness of BC cases that are negative for HER protein overexpression/gene amplification and the related clinical relevance for targeted therapy highlight the importance of accurate HER2 IHC scoring for optimal treatment selection.© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.