Department of Pathology, Wexner Medical Center at The Ohio State University, 410 W. 10th Ave, Columbus, OH, 43210, USA.
Roche Tissue Diagnostics, 1910 E. Innovation Park Drive, Tucson, AZ, 85755, USA.
Breast Cancer Res Treat. 2020 Jun;181(3):519-527. doi: 10.1007/s10549-020-05650-1. Epub 2020 Apr 25.
Human epidermal growth factor receptor 2 (HER2) intratumoral heterogeneity (ITH) occurs in a subset of breast cancers. Our recent study revealed it as an independent predictive factor for the response to anti-HER2 neoadjuvant therapy. In this study, we aimed to investigate its association with distal metastasis.
HER2 ITH was assessed using HER2 gene protein assay (GPA) on whole tissue sections of pretreatment biopsies from a cohort of 158 HER2-positive invasive breast carcinomas and correlated with patients' clinical follow-up outcomes along with other clinicopathologic characteristics.
Fifty-seven cases (36%) showed HER2 ITH including 19 with genetic, 8 with both genetic and non-genetic, and 30 with non-genetic ITH. Multivariate analysis demonstrated larger tumor size, positive resected lymph node(s), negative PR, and the presence of HER2 ITH were independently associated with distal metastasis. Additionally, multivariate analysis demonstrated larger tumor size and the presence of HER2 ITH were the only independent factors associated with decreased overall survival (death).
The presence of HER2 ITH is an independent factor associated with poor overall survival and increased distal metastasis in HER2-positive breast cancer patients.
人表皮生长因子受体 2（HER2）肿瘤内异质性（ITH）发生于一部分乳腺癌中。我们最近的研究表明，其是抗 HER2 新辅助治疗反应的独立预测因素。在本研究中，我们旨在探讨其与远处转移的相关性。
采用 HER2 基因蛋白检测（GPA）对 158 例 HER2 阳性浸润性乳腺癌患者的预处理活检全组织切片进行 HER2 ITH 评估，并与患者的临床随访结果及其他临床病理特征进行相关性分析。
57 例（36%）存在 HER2 ITH，其中 19 例存在基因 ITH，8 例存在基因和非基因 ITH，30 例存在非基因 ITH。多因素分析表明，肿瘤较大、阳性淋巴结切除、PR 阴性和存在 HER2 ITH 与远处转移独立相关。此外，多因素分析表明，肿瘤较大和存在 HER2 ITH 是与总生存（死亡）降低相关的唯一独立因素。
HER2 ITH 的存在是与 HER2 阳性乳腺癌患者总生存不良和远处转移增加相关的独立因素。
