Immune marker expression and prognosis of early breast cancer expressing HER3

IF 7.6 1区 医学 Q1 ONCOLOGY European Journal of Cancer Pub Date : 2024-10-20 DOI:10.1016/j.ejca.2024.115081
Dae-Won Lee , Han Suk Ryu , Ilias P. Nikas , Jiwon Koh , Tae-Yong Kim , Hong Kyu Kim , Han-Byoel Lee , Hyeong-Gon Moon , Wonshik Han , Kyung-Hun Lee , Seock-Ah Im
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Abstract

Introduction

There is a strong rationale for targeting HER3, as HER3 contributes to tumorigenesis and treatment resistance. However, the prognostic role of HER3 and their association with immunoregulatory protein expression has not been established.

Methods

The main objective of this study was to investigate the prognostic role of HER3 expression and identify immunoregulatory marker expression according to HER3 status. HER3 expression and 10 immunoregulatory protein (PD-1/PD-L1/PD-L2/IDO/TIM-3/OX40/OX40L/B7-H2/B7-H3/B7-H4) expression was identified in 320 stage I-III breast cancer patients who received curative surgery at Seoul National University Hospital in 2008. The median follow-up duration was 88.8 months. Criteria for HER3 IHC was adopted from HER2 IHC score and only those with 3 + was considered positive.

Results

Among 320 patients, 213 (67.2 %) had luminal A disease, 30 (9.5 %) had luminal B disease, 28 (8.8 %) had HER2-positive disease, and 46 (14.5 %) had triple negative disease. HER3 expression was shown in 153 patients (47.8 %). Tumors with HER3-expression had more immunogenic tumor microenvironment compared to HER3-negative tumor. In addition, patients with HER3 expression had favorable 5-year relapse free survival compared to HER3-negative patients (5-year RFS 92.5 % vs. 85.2 %, p = 0.038). However, in the multivariate analysis, HER3 expression was not a prognostic factor, but expression of immunoregulatory protein was a prognostic factor.

Conclusions

This study identified immunoregulatory protein expression according to HER3 status in breast cancer patients. As tumor with HER3 expression have more immunogenic microenvironment, investigating combination treatment of HER3 targeting agent and immunotherapy in HER3 expressing breast cancer may be promising.
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表达 HER3 的早期乳腺癌的免疫标记表达和预后。
导言:以 HER3 为靶点有很强的合理性,因为 HER3 会导致肿瘤发生和耐药性。然而,HER3的预后作用及其与免疫调节蛋白表达的关联尚未确定:本研究的主要目的是研究 HER3 表达的预后作用,并根据 HER3 状态确定免疫调节标志物的表达。2008年,在首尔国立大学医院接受根治性手术的320名I-III期乳腺癌患者中,HER3表达和10种免疫调节蛋白(PD-1/PD-L1/PD-L2/IDO/TIM-3/OX40/OX40L/B7-H2/B7-H3/B7-H4)表达得到了确认。中位随访时间为 88.8 个月。HER3 IHC 的标准采用 HER2 IHC 的评分,只有 3 + 的患者才被视为阳性:在 320 例患者中,213 例(67.2%)为管腔 A 型疾病,30 例(9.5%)为管腔 B 型疾病,28 例(8.8%)为 HER2 阳性疾病,46 例(14.5%)为三阴性疾病。153名患者(47.8%)有HER3表达。与HER3阴性肿瘤相比,HER3表达的肿瘤具有更强的免疫原性肿瘤微环境。此外,与 HER3 阴性患者相比,HER3 表达患者的 5 年无复发生存率更高(5 年 RFS 92.5% 对 85.2%,P = 0.038)。然而,在多变量分析中,HER3表达不是预后因素,但免疫调节蛋白的表达是预后因素:这项研究根据乳腺癌患者的 HER3 状态确定了免疫调节蛋白的表达。由于HER3表达的肿瘤具有更强的免疫原性微环境,研究HER3靶向药物和免疫疗法联合治疗HER3表达的乳腺癌可能很有前景。
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
European Journal of Cancer 医学-肿瘤学
CiteScore
11.50
自引率
4.80%
发文量
953
审稿时长
23 days
期刊介绍: The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.
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