HER2 testing in multifocal/multicentric breast cancer: should all foci be tested in the context of HER2-low and HER2-ultralow?

IF 7.9 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Breast Pub Date : 2025-09-13 DOI:10.1016/j.breast.2025.104572

Si Wu , Hongbo Liu , Tianyu Wang, Jiaxian Miao, Jiamei Zhuan, Zhongze Cui, Meng Yue, Kun Wang, Jinze Li, Mengxue Han, Wenhan Hu, Xiaoxiao Wang, Yueping Liu

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引用次数: 0

Abstract

Background

Current guidelines for HER2 testing in multifocal and multicentric breast cancer (MMBC) are typically based only on the evaluation of the main focus, which may lead to underdetection of HER2-low and HER2-ultralow, potentially resulting in missed treatment opportunities with trastuzumab deruxtecan. Therefore, this study aimed to evaluate the heterogeneity of HER2 expression among different foci in MMBC and to assess the clinical applicability of current HER2 testing strategies.

Methods

A retrospective collection of all invasive cancer foci specimens was conducted from 490 consecutive MMBC patients, with HER2 testing and evaluation performed on each individual focus.

Results

In the binary classification of HER2-negative and HER2-positive cases, 4.0 % of cases exhibited HER2 discordance among different foci, and in 2.5 % of cases, the main focus did not show the highest HER2 expression. However, when HER2-negative cases were further subdivided into HER2-null, HER2-ultralow, and HER2-low, 23.7 % of cases demonstrated HER2 heterogeneity among different foci, and in 12.0 % of cases, the main focus failed to present the highest HER2 expression. And no statistically significant correlation was observed between clinicopathological characteristics and the lack of highest HER2 expression in the main focus. Additionally, cases in which all foci were HER2-null accounted for only 11.0 %.

Conclusion

In MMBC, significant intertumoral heterogeneity exists in the low levels of HER2 expression across different foci. Therefore, it is essential to perform HER2 testing on all foci, regardless of similarities in histological subtype or grade.

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多灶/多中心乳腺癌的HER2检测：是否所有灶都应在HER2低和HER2超低的情况下进行检测？

背景：目前针对多灶多中心乳腺癌（MMBC）的HER2检测指南通常仅基于对主要病灶的评估，这可能导致HER2低和HER2超低的检测不足，从而可能导致错失曲妥珠单抗德鲁德替康的治疗机会。因此，本研究旨在评估MMBC中不同部位HER2表达的异质性，并评估当前HER2检测策略的临床适用性。方法：回顾性收集490例连续MMBC患者的所有浸润性癌灶标本，对每个病灶进行HER2检测和评估。结果：在HER2阴性和HER2阳性的二元分类中，4.0%的病例在不同灶间表现出HER2不一致，2.5%的病例在主灶上没有最高的HER2表达。然而，当HER2阴性病例进一步细分为HER2-null、HER2-超低和HER2-低时，23.7%的病例在不同灶间表现出HER2异质性，12.0%的病例主灶未能表现出最高的HER2表达。临床病理特征与主要病灶缺乏最高HER2表达无统计学意义相关。此外，所有病灶均为her2阴性的病例仅占11.0%。结论：在MMBC中，不同病灶的HER2低水平表达存在显著的肿瘤间异质性。因此，无论组织学亚型或分级是否相似，对所有病灶进行HER2检测都是必要的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Breast 医学-妇产科学

CiteScore

8.70

自引率

2.60%

发文量

165

审稿时长

59 days

期刊介绍： The Breast is an international, multidisciplinary journal for researchers and clinicians, which focuses on translational and clinical research for the advancement of breast cancer prevention, diagnosis and treatment of all stages.