Molecular and clinical traits of HER2-low breast cancer patients and their relationship with neoadjuvant treatment effectiveness.

IF 2.1 4区医学 Q3 ONCOLOGY

European Journal of Cancer Prevention Pub Date : 2025-05-01 Epub Date: 2024-09-16 DOI:10.1097/CEJ.0000000000000924

Wei Zhao, Mingxiang Zhang, Bohui Zhu, Yueyin Pan, Yiyuan Sun

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引用次数: 0

Abstract

Background: We aimed to investigate the clinical and molecular characteristics of different degrees of human epidermal growth factor receptor 2 (HER2) protein expression in HER2-negative breast cancer and the related factors affecting the efficacy of neoadjuvant chemotherapy in HER2-low breast cancer patients.

Methods: The study endpoint was pathological complete remission (PCR). Blood specimens and fresh cancer tissue samples were collected before neoadjuvant chemotherapy for whole-exon sequencing (WES) and RNA sequencing (RNA-seq), and patients were divided into a human epidermal growth factor receptor 2 (HER2)-low group and a HER2-0 group according to their HER2 expression status via bioinformatics analysis.

Results: A total of 409 HER2-negative breast cancer patients were included in the analysis, and HER2 status (HER2-0 vs. HER2-low) was significantly different between hormone receptor status, the Ki-67 index, and the PCR rate. A total of 18 patients who underwent WES and RNA testing were included, and the WES results suggested that the HER2-low group had a significantly higher rate of PIK3CA mutations and a greater frequency of PI3K pathway variants than the other groups and the HER2-low group had a greater number of concomitant mutations and reached statistical significance ( P = 0.03). In terms of expression profiles, HER2-low and HER2-0 patients had different expression profiles. Overall, suggesting that the low PCR rate in the HER2-low group may also be related to chemoresistance.

Conclusion: Our investigation highlights the possibility that HER2-low breast cancer may indicate a unique clinical and biological phenomenon.

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低her2乳腺癌患者的分子和临床特征及其与新辅助治疗效果的关系

背景：我们旨在探讨人表皮生长因子受体2 （HER2）蛋白在HER2阴性乳腺癌中不同程度表达的临床及分子特征，以及影响HER2低水平乳腺癌患者新辅助化疗疗效的相关因素。方法：以病理完全缓解（PCR）为研究终点。在新辅助化疗前采集血液标本和新鲜肿瘤组织标本，进行全外显子测序（WES）和RNA测序（RNA-seq），并根据HER2表达情况进行生物信息学分析，将患者分为人表皮生长因子受体2 （HER2）低表达组和HER2-0组。结果：共纳入409例HER2阴性乳腺癌患者，HER2状态（HER2-0 vs HER2-low）在激素受体状态、Ki-67指数、PCR率之间存在显著差异。我们共纳入了18例进行WES和RNA检测的患者，WES结果显示HER2-low组的PIK3CA突变率和PI3K通路变异频率明显高于其他组，HER2-low组的伴随突变数量较多，差异有统计学意义（P = 0.03）。在表达谱方面，HER2-low和HER2-0患者具有不同的表达谱。总之，提示her2低组的低PCR率也可能与化疗耐药有关。结论：我们的研究强调了her2低乳腺癌可能是一种独特的临床和生物学现象。

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

European Journal of Cancer Prevention 医学-肿瘤学

CiteScore

4.10

自引率

4.20%

发文量

审稿时长

1 months

期刊介绍： European Journal of Cancer Prevention aims to promote an increased awareness of all aspects of cancer prevention and to stimulate new ideas and innovations. The Journal has a wide-ranging scope, covering such aspects as descriptive and metabolic epidemiology, histopathology, genetics, biochemistry, molecular biology, microbiology, clinical medicine, intervention trials and public education, basic laboratory studies and special group studies. Although affiliated to a European organization, the journal addresses issues of international importance.