HER2 2+/FISH阴性对老年HER2阴性高危乳腺癌患者预后的不良影响

Unfavorable Prognostic Impact of HER2 2+/FISH-Negativity in Older Patients with HER2-Negative and High-Risk Breast Cancer.

作者信息

Wang Hao, Yu Miao, Chen Meihua, Li Hui, Liu Shiwei

机构信息

Department of Breast, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610042, People's Republic of China.

Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610042, People's Republic of China.

出版信息

Breast Cancer (Dove Med Press). 2024 Nov 19;16:785-793. doi: 10.2147/BCTT.S495183. eCollection 2024.

DOI:10.2147/BCTT.S495183

PMID:39588273

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11586453/

Abstract

PURPOSE

Human epidermal growth factor receptor 2 (HER2)-low breast cancer, consisted of carcinomas with HER2 protein 1+ or 2+ without gene amplification, has been considered a biologically heterogeneous disease. Limited research separately investigated the prognostic significance of HER2 2+ without gene amplification, and no evidence can be identified in older patients. In this dedicated cohort of older patients with HER2-negative and high-risk breast cancer, we analyzed the real-world prognosis after standard adjuvant chemotherapy, and investigated the associations of survival with HER2 2+ without gene amplification.

PATIENTS AND METHODS

From January 2016 to December 2021, older patients (≥65 years) with breast cancer were reviewed, and HER2-negative/high-risk disease receiving standard adjuvant chemotherapy was included. HER2-negativity was defined as immunohistochemistry (IHC) score 0, 1+ or 2+ without gene amplification by fluorescent in situ hybridization (FISH). Cox proportional hazards regression analyses were performed to assess the associations of HER2 2+/FISH-negativity with disease-free survival (DFS), which was estimated by the Kaplan-Meier method and compared by the Log rank test.

RESULTS

This cohort consisted of 121 consecutive older patients. With a median follow-up of 46 months, 12 patients had a DFS event. By univariate and multivariate analyses, HER2 2+/FISH-negativity was the only independent predictor for worse DFS (hazard ratio 5.56; =0.046). Patients with HER2 2+/FISH-negativity had significantly poorer DFS compared with those with HER2 0 or 1+ (Log rank test, =0.029). In both hormone receptor (HR)-positive (Log rank test, =0.052) and HR-negative (Log rank test, =0.125) subgroups, HER2 2+/FISH-negativity showed a marginally significant adverse influence on DFS.

CONCLUSION

In older patients with HER2-negative/high-risk breast cancer undergoing standard adjuvant chemotherapy, our findings suggest that HER2 2+/FISH-negativity has an independent negative impact on prognosis.

摘要

目的

人表皮生长因子受体2（HER2）低表达乳腺癌包括HER2蛋白1+或2+且无基因扩增的癌，被认为是一种生物学异质性疾病。有限的研究分别调查了无基因扩增的HER2 2+的预后意义，在老年患者中未发现相关证据。在这个专门的老年HER2阴性高危乳腺癌队列中，我们分析了标准辅助化疗后的真实世界预后，并研究了无基因扩增的HER2 2+与生存的相关性。

患者和方法

回顾2016年1月至2021年12月期间的老年（≥65岁）乳腺癌患者，纳入接受标准辅助化疗的HER2阴性/高危疾病患者。HER2阴性定义为免疫组织化学（IHC）评分为0、1+或2+且荧光原位杂交（FISH）无基因扩增。进行Cox比例风险回归分析以评估HER2 2+/FISH阴性与无病生存期（DFS）的相关性，DFS通过Kaplan-Meier法估计并通过对数秩检验进行比较。

结果

该队列包括121例连续的老年患者。中位随访46个月，12例患者出现DFS事件。通过单因素和多因素分析，HER2 2+/FISH阴性是DFS较差的唯一独立预测因素（风险比5.56；P = 0.046）。HER2 2+/FISH阴性的患者与HER2 0或1+的患者相比，DFS明显更差（对数秩检验，P = 0.029）。在激素受体（HR）阳性（对数秩检验，P = 0.052）和HR阴性（对数秩检验，P = 0.125）亚组中，HER2 2+/FISH阴性对DFS均显示出边缘显著的不利影响。