Department of Biomedical Sciences, Humanitas University, 20072, Pieve Emanuele, MI, Italy.
Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, 20089, Rozzano, MI, Italy.
Breast Cancer Res Treat. 2024 Feb;203(3):487-495. doi: 10.1007/s10549-023-07151-3. Epub 2023 Nov 4.
HER2-low breast cancer (BC) is a novel entity with relevant therapeutic implications, especially in hormone receptor (HR) positive BC. This study examines whether HER2 mRNA through the 21-gene assay, Oncotype DX (ODX), can refine the diagnosis of HER2-low and HER2-zero, obtained by immunohistochemistry (IHC).
Between Jan 2021 and Jan 2023, 229 consecutive HR-positive HER2-negative early BC (T1-3 N0-1) have been characterised by IHC and ODX. HER2 status by IHC was either zero (IHC-0) or low (IHC-1 + and IHC-2 + /ISH-negative) while HER2-zero was further divided into HER2-null (IHC-0) and HER2-ultralow (IHC-1-10%). HER2 gene expression by ODX was negative if lower 10.7.
The distribution of HER2 IHC was as follows: 53.3% HER2-0, 29.25% HER2-1 + , and 17.5% HER2-2 + . The clinicopathological characteristics were similar in the three groups, with higher PgR-negative rate in HER2-zero (13.9% vs 3% vs 5%). The distribution of RS was homogeneous in the three groups with the median HER2 gene expression of 9.20 [IQR: 8.70-9.60]. HER2 gene expression gradually increased as the IHC score, with substantial overlap. After adjusting for confounders, HER2-1 + and HER2 2 + had a significant positive correlation between HER2 gene expression and IHC [OR 1.42, 95% CI 1.21 to 1.68, p < 0.001; OR 1.96, 95% CI 1.61 to 2.37, p < 0.001] compared to the HER2-zero group. HER2 gene expression did not differ between HER2-null and HER2-ultralow subgroups.
Due to the substantial overlap, the HER2 gene expression is unable to properly distinguish HER2-low and HER2-zero IHC whose accurate identification is critical in the context of HER2-negative BC.
HER2 低表达乳腺癌（BC）是一种具有相关治疗意义的新实体，特别是在激素受体（HR）阳性 BC 中。本研究旨在探讨通过 21 基因检测（Oncotype DX，ODX）检测的 HER2 mRNA 是否可以改善免疫组织化学（IHC）检测的 HER2 低表达和 HER2 零表达的诊断。
2021 年 1 月至 2023 年 1 月期间，连续入组 229 例 HR 阳性 HER2 阴性早期 BC（T1-3N0-1）患者，对其进行 IHC 和 ODX 检测。HER2 状态通过 IHC 检测，分为零（IHC-0）、低（IHC-1+和 IHC-2+/ISH 阴性），而 HER2 零进一步分为 HER2 缺失（IHC-0）和 HER2 超低表达（IHC-1-10%）。ODX 检测的 HER2 基因表达如果低于 10.7，则为阴性。
HER2 IHC 的分布如下：53.3% HER2-0、29.25% HER2-1+、17.5% HER2-2+。三组的临床病理特征相似，HER2 零组的孕激素受体（PgR）阴性率更高（13.9% vs 3% vs 5%）。三组的 RS 分布均匀，中位 HER2 基因表达为 9.20[IQR：8.70-9.60]。随着 IHC 评分的增加，HER2 基因表达逐渐增加，存在显著重叠。调整混杂因素后，HER2-1+和 HER2 2+与 HER2 零组相比，HER2 基因表达与 IHC 呈显著正相关[OR 1.42，95%CI 1.21-1.68，p<0.001；OR 1.96，95%CI 1.61-2.37，p<0.001]。HER2 零组与 HER2 缺失和 HER2 超低表达亚组之间的 HER2 基因表达无差异。
由于存在显著重叠，HER2 基因表达无法正确区分 HER2 低表达和 HER2 零表达，而准确识别这两种情况在 HER2 阴性 BC 中至关重要。
