低HER2表达对晚期HR + /HER2-乳腺癌患者CDK4/6抑制剂治疗反应的影响：一项多中心真实世界数据分析

Impact of low HER2 expression on response to CDK4/6 inhibitor treatment in advanced HR + /HER2- breast cancer: a multicenter real-world data analysis.

作者信息

Ralser Damian J, Kiver Verena, Solomayer Erich-Franz, Neeb Caroline, Blohmer Jens-Uwe, Abramian Alina V, Maass Nicolai, Schütz Florian, Kolberg-Liedtke Cornelia, Müller Carolin, Rambow Anna-Christina

机构信息

Department of Gynecology and Gynecological Oncology, University Hospital Bonn, University Medical Center Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Department of Gynecology With Breast Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.

出版信息

Arch Gynecol Obstet. 2025 Feb;311(2):423-427. doi: 10.1007/s00404-024-07761-2. Epub 2024 Oct 7.

DOI:10.1007/s00404-024-07761-2

PMID:39373732

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11890318/

Abstract

PURPOSE

CDK4/6 inhibitors (CDK4/6i) represent the first-line therapy approach of choice for patients with hormone receptor-positive, HER2-negative advanced breast cancer (HR + /HER-ABC). Approximately 50% of HR + /HER2-ABC displays low HER2 expression (HER2 low). Recent data emerging from the DESTINY-Breast04 trial demonstrated practice-changing efficacy of the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in patients with low HER2 expression. Here, we aimed to analyze the impact of low HER2 expression on CDK4/6i therapy response in a well-characterized multicenter HR + /HER-ABC cohort.

METHODS

Patients diagnosed with HR + /HER2-ABC who were treated with CDK4/6i in clinical routine between November 2016 and December 2020 at four certified German Breast Cancer Centers were retrospectively identified. The cohort was stratified according to graduation of positivity in HER2 immunohistochemistry (IHC; HER2 zero = IHC score 0 and HER2 low = IHC score 1 + , 2 + /fluorescence in situ hybridization negative). Subgroups were analyzed with regard to progression-free survival (PFS) following CDK4/6i initiation.

FINDINGS

The study cohort comprised n = 448 patients. For n = 311 patients, HER2 status from the metastatic site was available. n = 91 (29.3%) cases were HER2 zero and n = 220 cases (70.7%) were HER2 low. There was no significant difference in PFS between the two groups (PFS: 17 months versus 18 months, log-rank p = 0.42). Further, we examined the influence of HER2 expression changes between primary and metastatic tissue (n = 171; HER2 gain/HER2 loss/HER2 stable expression) on CDK4/6i treatment response. Again, there was no significant difference between these three groups, respectively (PFS: 16 months versus 13 months versus 17 months, log-rank p = 0.86).

CONCLUSIONS

In our analysis, HER2 status did not have a significant impact on treatment response to CDK4/6i.

摘要

目的

细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）是激素受体阳性、人表皮生长因子受体2阴性晚期乳腺癌（HR + /HER-ABC）患者的一线首选治疗方法。约50%的HR + /HER2-ABC表现为HER2低表达（HER2 low）。DESTINY-Breast04试验的最新数据显示，抗体药物偶联物德曲妥珠单抗（T-DXd）对HER2低表达患者具有改变临床实践的疗效。在此，我们旨在分析HER2低表达对一个特征明确的多中心HR + /HER-ABC队列中CDK4/6i治疗反应的影响。

方法

回顾性确定2016年11月至2020年12月期间在德国四个认证乳腺癌中心接受CDK4/6i临床常规治疗的HR + /HER2-ABC患者。根据HER2免疫组化阳性程度对队列进行分层（HER2零表达=免疫组化评分为0，HER2低表达=免疫组化评分为1+、2+/荧光原位杂交阴性）。分析亚组在开始使用CDK4/6i后的无进展生存期（PFS）。

结果

研究队列包括448例患者。311例患者可获得转移部位的HER2状态。91例（29.3%）为HER2零表达，220例（70.7%）为HER2低表达。两组之间的PFS无显著差异（PFS：17个月对18个月，对数秩检验p = 0.42）。此外，我们研究了原发组织和转移组织之间HER2表达变化（n = 171；HER2增加/HER2减少/HER2稳定表达）对CDK4/6i治疗反应的影响。同样，这三组之间也无显著差异（PFS：16个月对13个月对17个月，对数秩检验p = 0.86）。