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

作者：Caroline Rönnlund, Emmanouil G. Sifakis, Caroline Schagerholm, Qiao Yang, Emelié Karlsson, Xinsong Chen, Theodoros Foukakis, Jodi Marie Weidler, Michael Bates, Irma Fredriksson, Stephanie Robertson, Johan Hartman · 发表于：Breast Cancer Research · 年份：2024 · DOI：10.1186/s13058-024-01779-9 · 被引用次数：6 · 研究领域：HER2/EGFR in Cancer Research、Breast Cancer Treatment Studies、Cancer Cells and Metastasis

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...