文章：

高HER2肿瘤内异质性是早期和局部晚期HER2阳性乳腺癌预后不良的预测因素

High HER2 Intratumoral Heterogeneity Is a Predictive Factor for Poor Prognosis in Early-Stage and Locally Advanced HER2-Positive Breast Cancer

原文发布日期：5 March 2024

DOI: 10.3390/cancers16051062

类型: Article

开放获取: 是

英文摘要：

Purpose: Breast cancer tumors frequently have intratumoral heterogeneity (ITH). Tumors with high ITH cause therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to a poor prognosis for HER2-targeted adjuvant therapy resistance in primary breast cancers. Methods: This study included patients with primary breast cancer (n= 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with the HER2 gene copy number within a tumor sample. Each tumor was classified into a biphasic grade graph (high heterogeneity [HH]) group or a monophasic grade graph (low heterogeneity [LH]) group based on heterogeneity. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. Results: Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS:p< 0.001 (HH:63% vs. LH:91% at 10 years) and for the OS:p= 0.012 (HH:78% vs. LH:95% at 10 years). Conclusions: High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach to heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

摘要翻译： 

目的：乳腺癌肿瘤常存在瘤内异质性。高瘤内异质性肿瘤可导致治疗抵抗，并在人表皮生长因子受体2靶向治疗中表现出HER2异质性。本研究旨在探讨原发性乳腺癌中，高HER2异质性水平是否与HER2靶向辅助治疗耐药导致的预后不良存在临床关联。方法：本研究纳入接受HER2靶向辅助治疗的原发性乳腺癌患者（n=251）。HER2异质性通过肿瘤样本内HER2基因拷贝数的荧光原位杂交扩增分布直方图形状来表征。根据异质性程度，将每个肿瘤分为双相分级图（高异质性组）或单相分级图（低异质性组）。两组均接受中位十年的年度随访，评估无病生存期和总生存期。结果：在251例HER2阳性乳腺癌患者中，46例（18.3%）和205例（81.7%）分别被归入高异质性组和低异质性组。与低异质性组相比，高异质性组具有更高的远处转移率和更差的预后（无病生存期：p<0.001，10年生存率分别为63% vs 91%；总生存期：p=0.012，10年生存率分别为78% vs 95%）。结论：高HER2异质性是HER2阳性乳腺癌患者的不良预后因素。基于HER2荧光原位杂交分布形状的新型异质性评估方法，可能在临床上有助于预测HER2辅助治疗后患者的预后。

原文链接：

High HER2 Intratumoral Heterogeneity Is a Predictive Factor for Poor Prognosis in Early-Stage and Locally Advanced HER2-Positive Breast Cancer