Faculty of Medicine, The Technion Institute of Technology, Haifa, Israel.
Department of Molecular Biology, Ariel University, Ariel, Israel.
BMC Cancer. 2023 Oct 24;23(1):1031. doi: 10.1186/s12885-023-11530-w.
One-half of hormone receptor-positive (HR +) breast cancer (BC) patients have low expression of HER2 (HER2-low) and may benefit from trastuzumab deruxtecan (TDXd). This study aimed to identify parameters associated with HER2-low levels in primary and metastatic tumors. We specifically sought to determine whether OncotypeDX and HER2 mRNA levels could identify patients who would otherwise be considered HER2-negative by immunohistochemistry (IHC).
This retrospective analysis of all consecutive HR + patients who underwent OncotypeDX from January 2004 to December 2020 was conducted in a single medical center (n = 1429). We divided HER2-negative cases into HER2-low (IHC = 1 + or 2 + and non-amplified fluorescent situ hybridization) and HER2-0 (IHC = 0). HER2 RT-PCR was evaluated from the OncotypeDX results.
HER2-low cases exhibited significantly higher HER2 RT-PCR scores (p = 2.1e-9), elevated estrogen receptor (ER) levels (p = 0.0114), and larger tumor sizes compared to HER2-0 cases (> 2 cm; 36.6% vs. 22.1%, respectively, p < 0.00001). Primary tumors > 2 cm were more likely to be HER2-low (OR = 2.07, 95% CI: 1.6317 to 2.6475, p < 0.0001). Metastatic BCs expressed higher HER2 IHC scores compared with primary BCs (Wilcoxon signed-rank, p = 0.046). HER2 IHC scores were higher for low-risk vs. medium-risk OncotypeDX (p = 0.0067). No other clinical or pathological parameters were associated with the increase in HER2 levels in the metastatic samples.
It might be beneficial to use clinical data from the primary tumor, including the HER2 RT-PCR score, to determine a HER2-low status.
一半的激素受体阳性（HR+）乳腺癌（BC）患者 HER2 表达水平较低（HER2-低），可能受益于曲妥珠单抗-德鲁替康（TDXd）。本研究旨在确定与原发和转移性肿瘤中 HER2 低水平相关的参数。我们特别旨在确定 OncotypeDX 和 HER2 mRNA 水平是否可以识别那些否则通过免疫组织化学（IHC）被认为是 HER2 阴性的患者。
这项回顾性分析了 2004 年 1 月至 2020 年 12 月期间在单一医疗中心接受 OncotypeDX 的所有连续 HR+患者（n=1429）。我们将 HER2 阴性病例分为 HER2-低（IHC=1+或 2+且非扩增荧光原位杂交）和 HER2-0（IHC=0）。从 OncotypeDX 结果评估 HER2 RT-PCR。
HER2-低病例的 HER2 RT-PCR 评分明显更高（p=2.1e-9），雌激素受体（ER）水平升高（p=0.0114），肿瘤大小也大于 HER2-0 病例（>2cm；分别为 36.6%和 22.1%，p<0.00001）。>2cm 的原发肿瘤更有可能是 HER2-低（OR=2.07，95%CI：1.6317 至 2.6475，p<0.0001）。转移性 BC 的 HER2 IHC 评分高于原发性 BC（Wilcoxon 符号秩检验，p=0.046）。低风险与中风险 OncotypeDX 的 HER2 IHC 评分更高（p=0.0067）。在转移性样本中，没有其他临床或病理参数与 HER2 水平的升高相关。
使用原发肿瘤的临床数据，包括 HER2 RT-PCR 评分，来确定 HER2-低状态可能是有益的。
