Hu Yan, Jones Dan, Zhao Weiqiang, Tozbikian Gary, Wesolowski Robert, Parwani Anil V, Li Zaibo
Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio.
Department of Internal Medicine, Medical Oncology Division, The Ohio State University Wexner Medical Center, Columbus, Ohio.
Mod Pathol. 2023 Jul;36(7):100164. doi: 10.1016/j.modpat.2023.100164. Epub 2023 Mar 24.
Human epidermal growth factor receptor 2 (HER2)-low breast cancer, defined by an immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization, is emerging as a predictive marker for the use of the antibody-drug conjugate. To understand how this category differs from HER2-zero cases, we investigated clinicopathological characteristics and HER2 fluorescence in situ hybridization results in a large cohort of 1309 continuous HER2-negative invasive breast carcinomas from 2018 to 2021 evaluated by the Food and Drug Administration-approved HER2 IHC test. Additionally, we compared Oncotype DX recurrence scores and HER2 mRNA expression between HER-low and HER2-zero cases in a separate cohort of 438 estrogen receptor-positive (ER+) early-stage breast carcinoma cases from 2014 to 2016. Based on the cohort from 2018 to 2021, the incidence of HER2-low breast cancers was approximately 54%. HER2-low cases had less frequent grade 3 morphology, less frequent triple-negative results, ER and progesterone receptor negativity, and a higher mean HER2 copy number and HER2/CEP17 ratio than HER2-zero cases (P < .0001). Among ER+ cases, HER2-low cases showed significantly less frequent Nottingham grade 3 tumors. In the cohort from 2014 to 2016, HER2-low cases showed significantly higher ER+ percentages, fewer progesterone receptor-negative cases, lower Oncotype DX recurrence scores, and higher HER2 mRNA expression scores than HER2-zero cases. In summary, this is the first study, to our knowledge, using a large cohort of continuous cases evaluated by the Food and Drug Administration-approved HER2 IHC companion diagnostic test for HER2-low expression and HER2 fluorescence in situ hybridization profile in a real-world setting. Although HER2-low cases showed a higher HER2 copy number, ratio, and mRNA level than HER2-zero cases statistically, such small differences are unlikely to be biologically or clinically meaningful. However, our study suggests that HER2-low/ER+ early-stage breast carcinoma may represent a less aggressive group of breast carcinoma, given its association with a lower Nottingham grade and Oncotype DX recurrence score.
人表皮生长因子受体2（HER2）低表达乳腺癌，定义为免疫组化（IHC）评分为1+或2+且原位杂交阴性，正逐渐成为使用抗体药物偶联物的预测标志物。为了解这一类别与HER2零表达病例有何不同，我们调查了2018年至2021年期间1309例连续的HER2阴性浸润性乳腺癌大样本队列的临床病理特征和HER2荧光原位杂交结果，这些病例通过了美国食品药品监督管理局批准的HER2 IHC检测。此外，我们在2014年至2016年的438例雌激素受体阳性（ER+）早期乳腺癌病例的单独队列中，比较了HER2低表达和HER2零表达病例之间的Oncotype DX复发评分及HER2 mRNA表达。基于2018年至2021年的队列，HER2低表达乳腺癌的发生率约为54%。与HER2零表达病例相比，HER2低表达病例的3级形态学发生率更低、三阴性结果更少、雌激素和孕激素受体阴性情况更少，且平均HER2拷贝数和HER2/CEP17比值更高（P <.0001）。在ER+病例中，HER2低表达病例的诺丁汉3级肿瘤发生率显著更低。在2014年至2016年的队列中，与HER2零表达病例相比，HER2低表达病例的ER+百分比显著更高、孕激素受体阴性病例更少、Oncotype DX复发评分更低，且HER2 mRNA表达评分更高。总之，据我们所知，这是第一项在现实环境中，使用通过美国食品药品监督管理局批准的HER2 IHC伴随诊断检测对大量连续病例进行评估，以分析HER2低表达及HER2荧光原位杂交特征的研究。尽管从统计学上看，HER2低表达病例的HER2拷贝数、比值和mRNA水平高于HER2零表达病例，但如此小的差异在生物学或临床上可能并无意义。然而，我们的研究表明，HER2低表达/ER+早期乳腺癌可能代表侵袭性较低的一组乳腺癌，因为其与较低的诺丁汉分级和Oncotype DX复发评分相关。
