Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Koto-ku, Tokyo.
Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Koto-ku, Tokyo.
ESMO Open. 2023 Aug;8(4):101582. doi: 10.1016/j.esmoop.2023.101582. Epub 2023 Jun 20.
According to the DESTINY-Breast04 trial, treating patients with breast cancer and low human epidermal growth factor receptor 2 expressions (HER2-low) varies from that of those with no HER2 expression. However, it is interesting to know if HER2-low indicates for anti-HER2 therapy in the gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Hence we conducted this study to assess the incidence, clinicopathological features, and treatment outcomes of patients with HER2-low G/GEJ adenocarcinoma.
This was a single-center, retrospective observational study. Patients with previously untreated G/GEJ adenocarcinoma were classified based on their HER2 status using immunohistochemistry (IHC) with or without in situ hybridization (ISH) as follows: HER2 negative (IHC 0), HER2-low (IHC 1+ or 2+/ISH-), and HER2-positive (IHC2+/ISH+ or 3+).
In total, 734 patients with G/GEJ adenocarcinoma were divided into three groups (HER2-negative, n = 410; HER2-low, n = 154, and HER2-positive, n = 170). The intestinal-type histology, peritoneal metastasis, and higher serum carcinoembryonic antigen (CEA) levels differed significantly among patients with negative, low, and positive HER2 statuses: intestinal-type histology (21.0%, 44.2%, and 59.8%, respectively), peritoneal metastasis (56.3%, 44.8%, and 21.8%, respectively), and higher serum CEA level (32.2%, 41.6%, and 56.5%, respectively). Improved survival was observed in the HER2-positive group than in the HER2-negative G/GEJ adenocarcinoma group [hazard ratio (HR) = 0.73, 95% confidence interval (CI) 0.59-0.89; P = 0.002]. However, the prognoses of the HER2-low and HER2-negative groups were similar (HR = 1.01, 95% CI 0.82-1.23; P = 0.843).
Patients with HER2-low G/GEJ adenocarcinoma exhibited intermediate and distinct characteristics than those in the HER2-negative group. Similarly, the HER2-low group's prognosis was worse than that of the HER2-positive group. Therefore developing novel therapeutic strategies targeting HER2-low G/GEJ adenocarcinoma is required.
根据 DESTINY-Breast04 试验，治疗人表皮生长因子受体 2 表达（HER2 低）的乳腺癌患者与无 HER2 表达的患者有所不同。然而，了解 HER2 低是否预示着胃或胃食管交界处（G/GEJ）腺癌需要抗 HER2 治疗，这很有趣。因此，我们进行了这项研究，以评估 HER2 低 G/GEJ 腺癌患者的发病率、临床病理特征和治疗结果。
这是一项单中心、回顾性观察性研究。根据免疫组织化学（IHC）和原位杂交（ISH）检测的 HER2 状态，将未经治疗的 G/GEJ 腺癌患者分为以下三组：HER2 阴性（IHC0）、HER2 低（IHC1+或 2+/ISH-）和 HER2 阳性（IHC2+/ISH+或 3+）。
共纳入 734 例 G/GEJ 腺癌患者，分为三组（HER2 阴性，n=410；HER2 低，n=154，HER2 阳性，n=170）。HER2 阴性、低表达和高表达患者的组织学类型、腹膜转移和血清癌胚抗原（CEA）水平差异显著：组织学类型（分别为 21.0%、44.2%和 59.8%）、腹膜转移（分别为 56.3%、44.8%和 21.8%）和血清 CEA 水平升高（分别为 32.2%、41.6%和 56.5%）。与 HER2 阴性 G/GEJ 腺癌组相比，HER2 阳性组的生存时间得到改善[风险比（HR）=0.73，95%置信区间（CI）0.59-0.89；P=0.002]。然而，HER2 低组和 HER2 阴性组的预后相似（HR=1.01，95%CI 0.82-1.23；P=0.843）。
HER2 低 G/GEJ 腺癌患者的特征与 HER2 阴性患者相似，但又有所不同。同样，HER2 低组的预后也比 HER2 阳性组差。因此，需要开发针对 HER2 低 G/GEJ 腺癌的新型治疗策略。
