Prognostic impact of HER2 biomarker levels in trastuzumab-treated early HER2-positive breast cancer.

IF 7.4 1区医学 Q1 Medicine

Breast Cancer Research Pub Date : 2024-02-07 DOI:10.1186/s13058-024-01779-9

Caroline Rönnlund, Emmanouil G Sifakis, Caroline Schagerholm, Qiao Yang, Emelie Karlsson, Xinsong Chen, Theodoros Foukakis, Jodi Weidler, Michael Bates, Irma Fredriksson, Stephanie Robertson, Johan Hartman

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Abstract

Background: Overexpression of human epidermal growth factor receptor 2 (HER2) caused by HER2 gene amplification is a driver in breast cancer tumorigenesis. We aimed to investigate the prognostic significance of manual scoring and digital image analysis (DIA) algorithm assessment of HER2 copy numbers and HER2/CEP17 ratios, along with ERBB2 mRNA levels among early-stage HER2-positive breast cancer patients treated with trastuzumab.

Methods: This retrospective study comprised 371 early HER2-positive breast cancer patients treated with adjuvant trastuzumab, with HER2 re-testing performed on whole tumor sections. Digitized tumor tissue slides were manually scored and assessed with uPath HER2 Dual ISH image analysis, breast algorithm. Targeted ERBB2 mRNA levels were assessed by the Xpert® Breast Cancer STRAT4 Assay. HER2 copy number and HER2/CEP17 ratio from in situ hybridization assessment, along with ERBB2 mRNA levels, were explored in relation to recurrence-free survival (RFS).

Results: The analysis showed that patients with tumors with the highest and lowest manually counted HER2 copy number levels had worse RFS than those with intermediate levels (HR = 2.7, CI 1.4-5.3, p = 0.003 and HR = 2.1, CI 1.1-3.9, p = 0.03, respectively). A similar trend was observed for HER2/CEP17 ratio, and the DIA algorithm confirmed the results. Moreover, patients with tumors with the highest and the lowest values of ERBB2 mRNA had a significantly worse prognosis (HR = 2.7, CI 1.4-5.1, p = 0.003 and HR = 2.8, CI 1.4-5.5, p = 0.004, respectively) compared to those with intermediate levels.

Conclusions: Our findings suggest that the association between any of the three HER2 biomarkers and RFS was nonlinear. Patients with tumors with the highest levels of HER2 gene amplification or ERBB2 mRNA were associated with a worse prognosis than those with intermediate levels, which is of importance to investigate in future clinical trials studying HER2-targeted therapy.

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曲妥珠单抗治疗的早期HER2阳性乳腺癌中HER2生物标志物水平的预后影响

背景：HER2基因扩增导致的人表皮生长因子受体2（HER2）过表达是乳腺癌肿瘤发生的驱动因素。我们旨在研究接受曲妥珠单抗治疗的早期 HER2 阳性乳腺癌患者中，HER2 拷贝数、HER2/CEP17 比值以及 ERBB2 mRNA 水平的人工评分和数字图像分析（DIA）算法评估的预后意义：这项回顾性研究包括371例接受曲妥珠单抗辅助治疗的早期HER2阳性乳腺癌患者，对整个肿瘤切片进行了HER2再检测。数字化肿瘤组织切片由人工评分，并使用 uPath HER2 双 ISH 图像分析乳腺算法进行评估。用 Xpert® 乳腺癌 STRAT4 检测法评估靶向 ERBB2 mRNA 水平。原位杂交评估得出的HER2拷贝数和HER2/CEP17比值以及ERBB2 mRNA水平与无复发生存期（RFS）的关系进行了探讨：分析结果显示，人工统计的HER2拷贝数水平最高和最低的肿瘤患者的无复发生存期（RFS）比水平居中的患者差（HR=2.7，CI 1.4-5.3，p=0.003；HR=2.1，CI 1.1-3.9，p=0.03）。HER2/CEP17比值也有类似趋势，DIA算法证实了这一结果。此外，与中等水平的肿瘤患者相比，ERBB2 mRNA值最高和最低的肿瘤患者预后明显较差（分别为HR = 2.7，CI 1.4-5.1，p = 0.003和HR = 2.8，CI 1.4-5.5，p = 0.004）：我们的研究结果表明，三种HER2生物标志物中的任何一种与RFS之间的关系都是非线性的。HER2基因扩增或ERBB2 mRNA水平最高的肿瘤患者的预后比水平居中的患者差，这一点在未来研究HER2靶向疗法的临床试验中具有重要意义。

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 Cancer Research ONCOLOGY-

CiteScore

12.00

自引率

0.00%

发文量

审稿时长

12 weeks

期刊介绍： Breast Cancer Research, an international, peer-reviewed online journal, publishes original research, reviews, editorials, and reports. It features open-access research articles of exceptional interest across all areas of biology and medicine relevant to breast cancer. This includes normal mammary gland biology, with a special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal covers preclinical, translational, and clinical studies with a biological basis, including Phase I and Phase II trials.