Kim Hongsik, Kim Ryul, Kim Hye Ryeon, Jo Hyunji, Kim Hana, Ha Sang Yun, Park Joon Oh, Park Young Suk, Kim Seung Tae
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Division of Hematology-Oncology, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, South Korea.
Front Oncol. 2022 Feb 14;12:834104. doi: 10.3389/fonc.2022.834104. eCollection 2022.
HER2 aberrations have been reported as a novel biomarker in HER2-directed therapy or as a prognostic marker in various tumor types. However, in advanced biliary tract cancer (BTC), there have been few studies regarding HER2 aberrations as a biomarker. We analyzed 121 advanced BTC patients who had been treated with Gemcitabine/Cisplatin (GP) as a 1st line therapy between November 2019 and April 2021. Next-generation sequencing (NGS), namely, HER2 aberrations was performed in all patients. The TruSight™ Oncology 500 assay from Illumina was used for the NGS panel. Among 121 patients with advanced BTC, HER2 aberrations were observed in 18 patients (14.9%). For subtypes of HER2 aberrations, point mutation was observed in 5 patients (27.8%), gene amplification in 11 patients (61.1%), and both point mutation and gene amplification in 2 patients (11.1%). The frequency of HER2 aberrations was significantly different according to the primary tumor (p = 0.009). In gallbladder cancer, HER2 aberrations were observed at a relatively high frequency (36.4%). The tumor response to GP did not differ between patients with and without HER2 aberrations (33.3%, vs. 26.2%, respectively, p = 0.571). The median progression-free survival (PFS) to GP was 4.7 months (95% CI, 4.0 to 5.5 months) in patients with HER2 aberrations and 7.0 months (95% CI, 5.2 to 8.8 months) without HER2 aberrations (p = 0.776). The median overall survival (OS) was not reached and not reached in patients with and without HER2 aberrations (p = 0.739), respectively. The univariate analysis for PFS to GP and OS showed that HER2 aberrations were not an independent factor for survival. This study showed that the HER2 aberrations were observed in 14.9% of advanced BTC and were not an independent biomarker for survival.
HER2畸变已被报道为HER2靶向治疗中的一种新型生物标志物，或在各种肿瘤类型中作为一种预后标志物。然而，在晚期胆管癌（BTC）中，关于HER2畸变作为生物标志物的研究很少。我们分析了2019年11月至2021年4月期间接受吉西他滨/顺铂（GP）作为一线治疗的121例晚期BTC患者。对所有患者进行了二代测序（NGS），即检测HER2畸变。使用Illumina公司的TruSight™ Oncology 500检测方法进行NGS检测。在121例晚期BTC患者中，18例（14.9%）观察到HER2畸变。对于HER2畸变的亚型，5例（27.8%）观察到点突变，11例（61.1%）观察到基因扩增，2例（11.1%）同时观察到点突变和基因扩增。HER2畸变的频率根据原发肿瘤不同而有显著差异（p = 0.009）。在胆囊癌中HER2畸变的观察频率相对较高（36.4%）。有或无HER2畸变的患者对GP的肿瘤反应无差异（分别为33.3%和26.2%，p = 0.571）。有HER2畸变的患者对GP的中位无进展生存期（PFS）为4.7个月（95%CI为4.0至5.5个月），无HER2畸变的患者为7.0个月（95%CI为5.2至8.8个月）（p = 0.776）。有或无HER2畸变的患者的中位总生存期（OS）均未达到（p = 0.739）。对GP的PFS和OS的单因素分析表明，HER2畸变不是生存的独立因素。本研究表明，14.9%的晚期BTC患者存在HER2畸变，且HER2畸变不是生存的独立生物标志物。
