Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, MI, USA.
Department of Hematology and Medical Oncology, Henry Ford Health System, Detroit, MI, USA.
Mod Pathol. 2021 Apr;34(4):720-734. doi: 10.1038/s41379-020-00728-z. Epub 2021 Jan 21.
HER2 (ERBB2) gene status serves as a strong predictive marker of response to HER2-targeted agents in invasive breast cancers, albeit with heterogeneous response. Our aim was to determine the distribution and prognosis of HER2 groups by fluorescent in situ hybridization (FISH) using the updated 2018 American Society of Clinical Oncology-College of American Pathologist (ASCO-CAP) guidelines. We identified 226 cases of equivocal or positive HER2 FISH invasive breast cancer (interpreted by ASCO-CAP guidelines at the time of reporting) who received HER2-targeted agents from 2006 to 2017. We subcategorized Group 1 further into three subgroups: low amplified (HER2/CEP17 ratio ≥ 2.0-2.99, mean HER2/cell 4.0-5.9), amplified (HER2/CEP17 ratio ≥ 2.0-2.99, mean HER2/cell ≥ 6), and excessive amplification (HER2/CEP17 ratio ≥ 3.0, mean HER2/cell ≥ 4.0). Outcomes studied were recurrence, metastasis, second breast primary, disease-specific survival (DSS), and overall survival (OS). Univariate analysis showed that the five categories of HER2 FISH were significantly associated with OS (p < 0.01), specifically higher HER2 amplification was associated with fewer deaths. HER2 FISH status also statistically significantly relates to DFS (p < 0.01) and metastasis (p = 0.01) but not with recurrence or second breast primary in our study. Tumor type and HER2 ISH Groups are independent predictors for both OS and DFS in our cohort. The proposed Group 1 subcategories were significantly associated with OS (p < 0.01) and DFS (p < 0.01), excessive HER2 amplification was associated with longer median survival. The Cox regression models showed better survival outcomes for the excessive amplification subgroup than the low amplified subgroup, with OS (hazard ratio = 0.63, 95% CI 0.42-0.93) and DFS (HR = 0.55, 95% CI 0.37-0.83). We demonstrated that in HER2 FISH Group 1 patients, high HER2 amplification was significantly associated with longer OS and DFS; these patients seem to benefit more from HER2-targeted regimens. We recommend reporting these Group 1 subcategories when assessing HER2 FISH.
HER2（ERBB2）基因状态是预测浸润性乳腺癌对 HER2 靶向药物反应的有力标志物，尽管存在异质性反应。我们的目的是使用更新的 2018 年美国临床肿瘤学会-美国病理学家协会（ASCO-CAP）指南通过荧光原位杂交（FISH）确定 HER2 组的分布和预后。我们鉴定了 226 例 2006 年至 2017 年接受 HER2 靶向药物治疗的可疑或阳性 HER2 FISH 浸润性乳腺癌（报告时按 ASCO-CAP 指南解读）。我们进一步将第 1 组分为三个亚组：低扩增（HER2/CEP17 比值≥2.0-2.99，平均 HER2/细胞 4.0-5.9）、扩增（HER2/CEP17 比值≥2.0-2.99，平均 HER2/细胞≥6）和过度扩增（HER2/CEP17 比值≥3.0，平均 HER2/细胞≥4.0）。研究的结果是复发、转移、第二原发性乳腺癌、疾病特异性生存率（DSS）和总生存率（OS）。单因素分析表明，HER2 FISH 的五个类别与 OS 显著相关（p<0.01），特别是更高的 HER2 扩增与更少的死亡相关。HER2 FISH 状态也与 DFS（p<0.01）和转移（p=0.01）显著相关，但与复发或第二原发性乳腺癌无关。在我们的研究中，肿瘤类型和 HER2 ISH 组是 OS 和 DFS 的独立预测因素。在我们的队列中，提出的第 1 组亚类与 OS（p<0.01）和 DFS（p<0.01）显著相关，过度的 HER2 扩增与更长的中位生存时间相关。Cox 回归模型显示，过度扩增亚组的生存结果优于低扩增亚组，OS（风险比=0.63，95%CI 0.42-0.93）和 DFS（HR=0.55，95%CI 0.37-0.83）。我们证明，在 HER2 FISH 第 1 组患者中，高 HER2 扩增与更长的 OS 和 DFS 显著相关；这些患者似乎从 HER2 靶向治疗中获益更多。我们建议在评估 HER2 FISH 时报告这些第 1 组亚类。
