He Jun, Liu Hongming, Dong Yansong, Hu Chengyu, Liang Han, Shou Diwen, Cao Dong, Du Yongxing, Shao Xinxin, Lu Yiming, Wang Haikuo, Tuo Chuanlei, Deng Jingyu, Zhang Rupeng, Wang Xuejun, Li Bin, Zhong Ning, Liu Yong, Zhong Yuxin, Gong Weihua
Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou 310058, China.
Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.
iScience. 2025 May 21;28(6):112710. doi: 10.1016/j.isci.2025.112710. eCollection 2025 Jun 20.
HER2 is a crucial biomarker in gastric cancer, influencing both treatment strategies and patient prognosis. A multicenter retrospective study was conducted, including 398 patients with locally advanced gastric cancer who received neoadjuvant treatment (NAT) followed by gastrectomy between 2018 and 2023 at three medical centers in China. Alterations in HER2 expression after NAT were detected in more than 40% of patients, with a higher rate of decreased expression (26.0%) compared to increased expression (17.3%). Multivariate analysis indicated that HER2 status at diagnosis significantly influenced HER2 expression alteration. Patients with HER2 IHC 2+ tumors before NAT demonstrated an increased tendency for HER2 expression alterations after NAT. Decreased HER2 expression was associated with improved recurrence-free survival and overall survival. PD-1/PD-L1 inhibitors and trastuzumab both increased pCR rates, but neither significantly impacted the rate of HER2 expression alterations among non-pCR patients. Reassessing HER2 status after NAT is essential for guiding HER2-targeted therapies.
HER2是胃癌中的一个关键生物标志物，影响治疗策略和患者预后。开展了一项多中心回顾性研究，纳入了398例局部晚期胃癌患者，这些患者于2018年至2023年在中国的三个医疗中心接受了新辅助治疗（NAT），随后接受了胃切除术。超过40%的患者在NAT后检测到HER2表达改变，与表达增加（17.3%）相比，表达降低的比例更高（26.0%）。多变量分析表明，诊断时的HER2状态显著影响HER2表达改变。NAT前HER2免疫组化2+肿瘤患者在NAT后HER2表达改变的趋势增加。HER2表达降低与无复发生存期和总生存期的改善相关。PD-1/PD-L1抑制剂和曲妥珠单抗均提高了病理完全缓解（pCR）率，但两者均未显著影响非pCR患者中HER2表达改变的发生率。NAT后重新评估HER2状态对于指导HER2靶向治疗至关重要。
