Department of Medical Oncology, Yale School of Medicine, Yale Cancer Center, New Haven, CT, USA.
Exact Sciences Corporation, Redwood City, CA, USA.
Oncologist. 2023 Oct 3;28(10):e973-e976. doi: 10.1093/oncolo/oyad249.
HER2 immunohistochemistry (IHC) reproducibility is suboptimal for HER-low cases (IHC 1+ or 2+).
The Yale cohort included 214 stages I-II estrogen receptor positive breast cancers with IHC scores 0, 1+, and 2+ and routine Oncotype DX Recurrence Score (RS) results. The Exact Sciences (ES) cohort included 9 57 624 patients who had an Oncotype DX RS assay that assigns HER2-negative, equivocal, or positive status based on HER2 mRNA levels.
HER2 mRNA levels varied across IHC categories but with increasing medians of 9.10 (n = 89), 9.20 (n = 71), and 9.45 (n = 54) in IHC 0, 1+, and 2+, respectively. 22.4% of HER2-low (1+/2+) cancer had RS > 25. Over 98% of HER-low cancers were HER2-negative by Oncotype DX assignment.
Cancers with higher mRNA levels exist within IHC 0 and low categories, most of the HER2-low patients by IHC have low RS indicating no benefit from current adjuvant chemotherapies.
HER2 免疫组织化学（IHC）在 HER-低表达病例（IHC 1+或 2+）中的重复性不理想。
耶鲁队列包括 214 例 I 期至 II 期雌激素受体阳性乳腺癌患者，IHC 评分 0、1+和 2+，以及常规的 Oncotype DX 复发评分（RS）结果。Exact Sciences（ES）队列包括 957624 例患者，他们接受了 Oncotype DX RS 检测，该检测根据 HER2 mRNA 水平将 HER2-阴性、不确定或阳性状态进行赋值。
HER2 mRNA 水平在 IHC 类别之间存在差异，但随着 IHC 0、1+和 2+的中位数分别为 9.10（n=89）、9.20（n=71）和 9.45（n=54）而逐渐升高。22.4%的 HER-低（1+/2+）癌症患者的 RS>25。超过 98%的 HER-低表达的癌症通过 Oncotype DX 检测为 HER2 阴性。
在 IHC 0 和低分类中存在更高 mRNA 水平的癌症，大多数 IHC 为 HER-低表达的患者的 RS 较低，表明目前的辅助化疗没有获益。
