State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases.
Department of Health Statistics, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health.
Int J Surg. 2023 May 1;109(5):1330-1341. doi: 10.1097/JS9.0000000000000370.
Human epidermal growth factor receptor 2 (HER2) is a well-developed therapeutic target in breast and gastric cancer (GC). However, the impact of HER2 on survival and benefit from fluorouracil-based adjuvant chemotherapy remains unclear in patients with GC.
This multicenter cohort study involved 5622 consecutive stage II/III GC patients. HER2 expression was assessed prospectively via immunohistochemistry (IHC). The staining intensity was graded on a scale of 0 to 3+. An IHC score of 2+or 3+was defined as high expression, and a score of 3+was defined as overexpression.
HER2 overexpression was independently associated with a lower 5-year overall survival (OS) in stage II [hazard ratio (HR), 2.10; 95% CI: 1.41-3.11], but not in stage III GC (HR, 1.00; 95% CI, 0.82-1.20). Further analysis revealed that stage II patients with high HER2 expression showed a poorer response to chemotherapy than stage II patients with low HER2 expression ( Pinteraction =0.024). The HRs for 5-year OS were 0.51 (95% CI, 0.38-0.70) for stage II patients with low HER2 expression, 0.58 (95% CI, 0.51-0.66) for stage III patients with low HER2 expression, 1.13 (95% CI, 0.61-2.09) for stage II patients with high HER2 expression, and 0.47 (95% CI, 0.36-0.61) for stage III patients with high HER2 expression.
Fluorouracil-based adjuvant chemotherapy is insufficient for stage II GC patients with high HER2 expression, indicating that prospective trials are required to validate alternative HER2-targeted adjuvant therapies in the individuals above.
人表皮生长因子受体 2（HER2）是乳腺癌和胃癌（GC）中一个成熟的治疗靶点。然而，在 GC 患者中，HER2 对生存和氟尿嘧啶为基础的辅助化疗获益的影响仍不清楚。
这项多中心队列研究纳入了 5622 例连续的 II/III 期 GC 患者。HER2 表达通过免疫组织化学（IHC）进行前瞻性评估。染色强度评分为 0 至 3+。IHC 评分 2+或 3+定义为高表达，评分 3+定义为过表达。
HER2 过表达与 II 期患者 5 年总生存率（OS）降低独立相关（风险比[HR]，2.10；95%CI：1.41-3.11），但与 III 期 GC 无关（HR，1.00；95%CI，0.82-1.20）。进一步分析显示，高 HER2 表达的 II 期患者对化疗的反应不如低 HER2 表达的 II 期患者（P 交互=0.024）。低 HER2 表达的 II 期患者 5 年 OS 的 HR 为 0.51（95%CI，0.38-0.70），低 HER2 表达的 III 期患者为 0.58（95%CI，0.51-0.66），高 HER2 表达的 II 期患者为 1.13（95%CI，0.61-2.09），高 HER2 表达的 III 期患者为 0.47（95%CI，0.36-0.61）。
氟尿嘧啶为基础的辅助化疗对高 HER2 表达的 II 期 GC 患者不足，表明需要前瞻性试验来验证上述个体中替代的 HER2 靶向辅助治疗。
