关于乳腺癌中匹配的原发肿瘤和脑转移瘤 (BrM) 之间 HER2 低表达动态的数据有限。 HER2 低表达已成为具有新兴颅内活性的高活性抗体药物缀合物的新治疗生物标志物。对 2003 年至 2023 年间在 NCI 指定中心就诊的转移性乳腺癌 (MBC) 和 BrM 患者进行了鉴定。 ASCO-CAP 指南将 HER2 表达定义为 HER2 阳性（3 ,2 /ISH 扩增）、HER2 低（1 ,2 /ISH 阴性）或 HER2-0。雌激素受体（ER）状态定义为ER≥1%。通过 Cox 比例风险模型进行多变量生存分析，确定从 BrM 切除时间到死亡或 3 种亚型之间最后一次随访的时间，控制 ER 和年龄。在 197 个匹配的原发和切除的 BrM 中，81% 在大脑中表现出 HER2 表达： 61% HER2 阳性，20% HER2 低，19% HER2-0。 HER2 阳性原发肿瘤的一致性较高，100% 保留 HER2 表达（97% 保留 HER2 表达，2.7% 转为 HER2 低表达）。 HER2-0 初选经常显示 BrM 中 HER2 增加至 HER2 低 (35%) 或 HER2 阳性 (5.4%) 状态。在 48 个 HER2 低的原发性肿瘤中，52% 的大脑 HER2 状态不一致，其中 21% 检测为 HER2 阳性，31% 检测为 HER2-0。在调整分析中，HER2 阳性 BrM 患者的死亡风险显着低于 HER2 低 BrM 患者（HR=0.41，P=0.0006）； HER2-0 和 HER2-low 之间没有观察到差异。在这项回顾性分析中，HER2 表达在乳腺癌 BrM 中很常见，强调需要改进的非侵入性诊断。 HER2-low 和 HER2-0 BrM 患者的生存率较低，存在未满足的临床需求。© 作者 2024。由牛津大学出版社代表神经肿瘤学会出版。

There are limited data regarding HER2-low expression dynamics between matched primary tumors and brain metastases (BrMs) in breast cancer. HER2-low expression has emerged as a new therapeutic biomarker for highly active antibody-drug conjugates with emerging intracranial activity.Patients with metastatic breast cancer (MBC) and BrMs seen at an NCI-designated center between 2003-2023 were identified. HER2 expression was defined as HER2-positive (3+,2+/ISH amplified), HER2-low (1+,2+/ISH negative), or HER2-0 by ASCO-CAP guidelines. Estrogen receptor (ER) status was defined as ER≥1%. Multivariate survival analyses by Cox proportional hazard models were determined from time of BrM resection to death or last follow-up between the 3 subtypes, controlling for ER and age.Among 197 matched primary and resected BrMs, 81% exhibited HER2 expression in the brain:61% HER2-positive, 20% HER2-low, and 19% HER2-0. Concordance was high in HER2-positive primary tumors with 100% retaining HER2 expression (97% retained HER2+ expression and 2.7% switched to HER2-low). HER2-0 primaries frequently showed HER2 gain in BrMs to HER2-low (35%) or HER2-positive (5.4%) status. Among 48 HER2-low primary tumors, 52% were discordant for HER2 status in the brain with 21% testing HER2-positive and 31% testing HER2-0. In adjusted analyses, patients with HER2-positive BrMs had significantly lower death risk than patients with HER2-low BrMs (HR=0.41, P=0.0006); no difference was observed between HER2-0 and HER2-low.In this retrospective analysis, HER2 expression is common in breast cancer BrMs, emphasizing the need for improved, non-invasive diagnostics. Patients with HER2-low and HER2-0 BrMs face inferior survival, presenting an unmet clinical need.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.