PDF(Pubmed)
Abstract：
Since the release of the DESTINY-Breast04 (DB-04) trial findings in June 2022, the field of pathology has seen a renaissance of HER2 as a predictive biomarker in breast cancer. The trial focused on patients with metastatic breast cancer who were classified as \"HER2-low,\" i.e., those with immunohistochemistry (IHC) HER2 1 + or 2 + and negative in situ hybridization (ISH) results. The study revealed that treating these patients with trastuzumab deruxtecan (T-DXd) instead of the oncologist\'s chosen chemotherapy led to outstanding improvements in survival. This has challenged the existing binary HER2 pathological classification system, which categorized tumors as either positive (overexpression/amplification) or negative, as per the ASCO/CAP 2018 guideline reaffirmed by ASCO/CAP 2023 guideline update. Given that DB-04 excluded patients with HER2 IHC score 0 status, the results of the ongoing DB-06 trial may shed further light on the potential benefits of T-DXd therapy for these patients. Roughly half of all breast cancers are estimated to belong to the HER2-low category, which does not represent a distinct or specific subtype of cancer. Instead, it encompasses a diverse group of tumors that exhibit clinical, morphological, immunohistochemical, and molecular variations. However, HER2-low offers a distinctive biomarker status that identifies a specific therapeutic regimen (i.e., T-DXd) linked to a favorable prognosis in breast cancer. This unique association emphasizes the importance of accurately identifying these tumors. Differentiating between a HER2 IHC score 0 and score 1 + has not been clinically significant until now. To ensure accurate classification and avoid misdiagnosis, it is necessary to adopt standardized procedures, guidelines, and specialized training for pathologists in interpreting HER2 expression in the lower spectrum. Additionally, the utilization of artificial intelligence holds promise in supporting this endeavor. Here, we address the current state of the art and unresolved issues in assessing HER2-low status, with a particular emphasis on the score 0. We explore the dilemma surrounding the exclusion of HER2-zero patients from potentially beneficial therapy based on traditional HER2 testing. Additionally, we examine the clinical context, considering that DB-04 primarily involved heavily pretreated late-stage metastatic breast cancers. We also delve into emerging evidence suggesting that extrapolating HER2-low status from the original diagnosis may lead to misleading results. Finally, we provide recommendations for conducting high-quality testing and propose a standardized pathology report in compliance with 2023 ASCO/CAP updates and 2023 ESMO consensus statements on HER2-low breast cancer.
摘要：
自2022年6月发布DESTINY-Breast04（DB-04）试验结果以来，病理学领域已经看到HER2作为乳腺癌预测生物标志物的复兴。该试验的重点是被分类为“低HER2”的转移性乳腺癌患者，\"即，免疫组织化学（IHC）HER21+或2+和阴性原位杂交（ISH）结果。研究表明，用曲妥珠单抗deruxtecan（T-DXd）代替肿瘤学家选择的化疗治疗这些患者可显著改善生存率。这对现有的二元HER2病理分类系统提出了挑战,将肿瘤分类为阳性（过表达/扩增）或阴性，根据ASCO/CAP2023指南更新重申的ASCO/CAP2018指南。鉴于DB-04排除了HER2IHC评分为0的患者，正在进行的DB-06试验的结果可能进一步揭示T-DXd治疗对这些患者的潜在益处.据估计，大约一半的乳腺癌属于低HER2类别。不代表癌症的独特或特定亚型。相反，它包括一组不同的肿瘤，表现出临床，形态学,免疫组织化学，和分子变异。然而,HER2-low提供了一种独特的生物标志物状态，可识别特定的治疗方案(即T-DXd）与乳腺癌的良好预后有关。这种独特的关联强调了准确识别这些肿瘤的重要性。到目前为止，HER2IHC评分0和评分1+之间的区别在临床上并不显著。为了确保分类准确，避免误诊，有必要采取标准化的程序，指导方针,并对病理学家进行专门培训，以解释较低光谱中的HER2表达。此外,人工智能的利用有望支持这一努力。这里,我们解决了评估HER2低状态的最新技术和未解决的问题，特别强调0分。基于传统的HER2检测，我们探讨了将HER2-零患者排除在潜在有益治疗之外的困境。此外,我们检查了临床背景，考虑到DB-04主要涉及大量预处理的晚期转移性乳腺癌。我们还深入研究了新出现的证据，表明从原始诊断推断HER2低状态可能会导致误导性结果。最后,我们为开展高质量检测提供建议,并根据2023年ASCO/CAP更新和2023年ESMO关于低HER2乳腺癌的共识声明提出标准化病理报告.
