Long-term prognostic significance of HER2-low and HER2-zero in node-negative breast cancer

医学 免疫组织化学 内科学 乳腺癌 曲妥珠单抗 精确检验 肿瘤科 比例危险模型 分级(工程) 人表皮生长因子受体2 胃肠病学 HER2/东北 队列 癌症 病理 生物 生态学
作者
Katrin Almstedt,Anne-Sophie Heimes,Franziska Kappenberg,Marco Johannes Battista,Hans‐Anton Lehr,Slavomir Krajnak,Antje Lebrecht,Mathias Gehrmann,Kathrin Stewen,Walburgis Brenner,W. Weikel,Jörg Rahnenführer,Jan G. Hengstler,Annette Hasenburg,Marcus Schmidt
出处
期刊:European Journal of Cancer [Elsevier BV]
卷期号:173: 10-19 被引量:59
标识
DOI:10.1016/j.ejca.2022.06.012
摘要

Recently, novel antibody--drug conjugates (ADCs) showed clinical activity in a subset of advanced human epidermal growth factor receptor 2 (HER2)-negative patients. We investigated the prognostic significance of HER2-low and HER2-zero tumours.The retrospective cohort study included 410 consecutive node-negative breast cancer patients without adjuvant systemic therapy treated between 1985 and 2000 (median follow-up: 16.73 [IQR 8.58-23.45] years). 351 (85.6%) were HER-2 negative and subdivided into HER2-zero (immunohistochemistry [IHC] score 0) and HER2-low (IHC score 1+ or 2+/in situ hybridisation [ISH]-negative). HER2 gene expression was available in 170 (48.4%) patients. Differences in HER2 status for immunohistochemistry, gene expression and clinico-pathologic parameters were assessed using Fisher's exact test, Pearson's correlation and Mann-Whitney test. Prognosis was investigated using the Kaplan-Meier method and Cox regression analyses.Of the 351 HER2-negative patients, 198 (56.4%) had HER2-low tumours and 153 (43.6%) were HER2-zero. Significant differences between HER2-zero and HER2-low tumours were found in histologic grading (P = 0.001), Ki-67 (P = 0.013) and HER2 gene expression (P = 0.002). HER2-low patients had significantly longer disease-free survival (DFS) (15-year rate: 67.5% [95% CI 61.0-74.7] vs. 47.3% [95% CI 39.9-56.1], P < 0.001) and overall survival (OS) (15-year rate: 75.4% [95% CI 69.4-81.9] vs. 66.8% [95% CI 59.5-74.9], P = 0.009). The OS difference was observed in hormone receptor (HR)-positive (P = 0.039) but not HR-negative (P = 0.086) tumours. The results of multivariable analyses confirmed the independent prognostic significance of HER2 status (DFS: HR, 0.546; 95% CI, 0.402-0.743; P < 0.001; OS: HR, 0.653; 95% CI, 0.458-0.932; P = 0.019).HER2-low patients had a better survival than HER2-zero patients.
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