Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, 4000 Cambridge Street, Mail Stop 3067, Kansas City, KS, 66160, USA.
Breast Cancer Res Treat. 2023 Oct;201(3):437-446. doi: 10.1007/s10549-023-07020-z. Epub 2023 Jul 12.
Low HER2 expression is emerging as an actionable target for the treatment of breast cancer (BC) with the antibody drug conjugate Trastuzumab deruxtecan. The aim of the study was to characterize the dynamics of HER2 expression during BC progression.
We evaluated the evolution of HER2 expression in 171 paired primary and metastatic BCs (pBCs/mBCs) by including the HER2-low category.
The proportions of HER2-low cases were 25.7% in pBCs and 23.4% in mBCs, respectively, while those of HER2-0 cases were 35.1% and 42.7%, respectively. The overall conversion rate between HER2-0 and HER2-low was 31.7%. HER2-low switching to HER2-0 was more frequent than the reverse (43.2% vs. 23.3%; P = 0.03). Two (3.3%) and 9 (20.5%) cases of pBCs with a HER2-0 and a HER2-low status, respectively, were converted to HER2-positive mBCs. In contrast, 10 (14.9%) HER2-positive pBCs were converted to HER2-0 and an identical number to HER2-low mBCs, respectively, significantly higher than that when compared to the HER2-0 to HER2-positive (P = 0.03), but not HER2-low to HER2-positive conversion. No significant difference was found when comparing the conversion rates among the common organs of relapse. Of the 17 patients with multiorgan metastases, 41.2% had discordance among the different sites of relapse.
HER2-low BCs constitute a heterogeneous group of tumors. Low HER2 expression is dynamic, with significant discordance between primary tumors and advanced disease as well as the distant sites of relapse. Repeat biomarker studies from advanced disease are warranted in making appropriate treatment plans in the pursuit of precision medicine.
低 HER2 表达正成为治疗乳腺癌（BC）的一个可操作靶点，抗体药物偶联物曲妥珠单抗 deruxtecan 为此提供了治疗方法。本研究的目的是描述 HER2 表达在 BC 进展过程中的变化动态。
通过纳入低 HER2 类别，我们评估了 171 对原发性和转移性 BC（pBCs/mBCs）中 HER2 表达的演变。
pBCs 和 mBCs 中 HER2 低水平病例的比例分别为 25.7%和 23.4%，而 HER2-0 病例的比例分别为 35.1%和 42.7%。HER2-0 和 HER2 低水平之间的总转化率为 31.7%。HER2 低水平向 HER2-0 的转换频率高于相反方向（43.2% vs. 23.3%；P=0.03）。分别有 2（3.3%）和 9（20.5%）例 pBCs 的 HER2-0 和 HER2 低状态分别转化为 HER2 阳性 mBCs。相比之下，10（14.9%）例 HER2 阳性 pBCs 分别转化为 HER2-0 和 HER2 低水平 mBCs，这一比例明显高于 HER2-0 向 HER2 阳性的转换（P=0.03），但与 HER2 低水平向 HER2 阳性的转换无差异。在比较常见的复发器官的转化率时，未发现显著差异。在 17 例多器官转移患者中，41.2%的患者在不同部位复发时存在不一致。
HER2 低水平 BC 是一组异质性肿瘤。低 HER2 表达是动态的，原发肿瘤和晚期疾病以及远处复发部位之间存在显著差异。在追求精准医学的过程中，需要对晚期疾病的生物标志物进行重复研究，以制定适当的治疗计划。
