Lamont Elizabeth B, Stein Emily, Tarantino Paolo, Tolaney Sara M, Ahlberg Corinne, Chinnathambu Krishna, Qi Jiezhi, Bilan Jackie, Davi Ruthie, Ensign Lisa
Medidata AI, Medidata Solutions, a Dassault Systèmes Company, 350 Hudson Street, New York, NY, 10014, USA.
Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, USA.
Breast Cancer Res Treat. 2025 Feb;210(1):11-14. doi: 10.1007/s10549-024-07581-7. Epub 2024 Dec 20.
The therapeutic importance of subsetting patients with HER2-negative breast cancer according to their tumors' cellular HER2 expression (e.g., HER2-low vs. HER2-0) is relatively new, stemming from the dramatic results of the DESTINY-04 trial which established HER2-low expression as actionable. Most prior observational research of traditionally HER2-negative patients suggests that tumor behavior and biology do not vary according to HER2-low vs. HER2-0 expression, though some studies suggest otherwise. Here we studied this question in women with metastatic breast cancer (MBC) who were treated with standard single agent chemotherapy in the setting of clinical trials carried out in the pre-DESTINY-04 era. After pooling data from 142 female patients with MBC across historic clinical trials and categorizing them according to HER2 expression (i.e., HER2-0 or HER2-low), we evaluated associations between HER2 expression and the outcomes of both progression-free survival (PFS) and overall survival (OS) with both Kaplan-Meier and Cox proportional hazards methods. Studying data from an era when quantifying amounts of tumor HER2 expression in HER2-negative patients was neither standardized nor clinically actionable, we found no meaningful clinical differences in PFS or OS according to HER2-low vs. HER2-0 status, supporting prior findings of no biologic differences.
根据肿瘤细胞HER2表达情况（例如，HER2低表达与HER2零表达）对HER2阴性乳腺癌患者进行亚组分类的治疗重要性相对较新，这源于DESTINY-04试验的显著结果，该试验确定HER2低表达具有可操作性。以往大多数针对传统HER2阴性患者的观察性研究表明，肿瘤行为和生物学特性不会因HER2低表达与HER2零表达而有所不同，尽管一些研究得出了相反的结论。在此，我们对转移性乳腺癌（MBC）女性患者进行了研究，这些患者在DESTINY-04试验之前的临床试验背景下接受了标准单药化疗。在汇总了142名MBC女性患者在既往临床试验中的数据，并根据HER2表达情况（即HER2零表达或HER2低表达）进行分类后，我们采用Kaplan-Meier法和Cox比例风险法评估了HER2表达与无进展生存期（PFS）和总生存期（OS）结果之间的关联。研究的数据来自一个HER2阴性患者肿瘤HER2表达量的量化既未标准化也不具有临床可操作性的时代，我们发现根据HER2低表达与HER2零表达状态，PFS或OS并无有意义的临床差异，这支持了之前关于无生物学差异的研究结果。
