Yoon Harry H, Lewis Mark A, Foster Nathan R, Sukov William R, Khan Maliha, Sattler Christopher A, Wiktor Anne E, Wu Tsung-Teh, Jenkins Robert B, Sinicrope Frank A
Department of Medical Oncology, Mayo Clinic, Rochester, MN.
Department of Medical Oncology, MD Anderson Cancer Center, Houston, TX.
Int J Cancer. 2016 Oct 1;139(7):1626-31. doi: 10.1002/ijc.30200. Epub 2016 Jun 10.
Although HER2-positive breast cancers demonstrate a propensity for central nervous system (CNS) metastasis, it is unknown whether other HER2-positive tumors, including adenocarcinomas of the esophagus/gastroesophageal junction (EAC), share this characteristic. Insight into this association may inform the development of HER2-targeted therapies that penetrate the blood-brain barrier. We examined HER2 overexpression and gene amplification in 708 patients with EAC who underwent curative-intent surgery during a time period (1980-1997) when no patient received HER2-targeted therapy. We identified patients whose site of first cancer recurrence was CNS and those who had a CNS relapse at any time. After a median follow-up of 61.2 months, 3.4% (24/708) of patients developed CNS relapse (all involved the brain). Patients with HER2-positive (vs -negative) primary tumors showed a higher 5-year cumulative incidence of CNS relapse as first recurrence (5.8% vs. 1.2%; p = 0.0058) and at any time (8.3% vs. 2.4%; p = 0.0062). In a multivariable model that included covariates previously associated with HER2 or with CNS relapse in breast cancer, HER2 positivity was the only variable that was statistically significantly associated with shorter time to CNS relapse as first recurrence (p = 0.0026) or at any time (hazard ratio 4.3 [95% confidence interval 1.8 to 10.3]; p = 0.001). These are the first data in a non-breast cancer to demonstrate an association between HER2 positivity and higher CNS relapse risk after surgery, and suggest that HER2-positive EACs have a predilection for CNS metastases.
尽管HER2阳性乳腺癌易于发生中枢神经系统（CNS）转移，但包括食管/胃食管交界腺癌（EAC）在内的其他HER2阳性肿瘤是否具有这一特征尚不清楚。深入了解这种关联可能有助于开发能够穿透血脑屏障的HER2靶向疗法。我们研究了708例接受根治性手术的EAC患者的HER2过表达和基因扩增情况，这些患者处于一个没有患者接受HER2靶向治疗的时期（1980 - 1997年）。我们确定了首次癌症复发部位为中枢神经系统的患者以及任何时候发生中枢神经系统复发的患者。中位随访61.2个月后，3.4%（24/708）的患者发生中枢神经系统复发（均累及脑部）。HER2阳性（与阴性相比）原发性肿瘤患者的中枢神经系统复发作为首次复发的5年累积发生率更高（5.8%对1.2%；p = 0.0058），且在任何时候的累积发生率也更高（8.3%对2.4%；p = 0.0062）。在一个多变量模型中，纳入了先前与乳腺癌中HER2或中枢神经系统复发相关的协变量，HER2阳性是唯一与首次复发（p = 0.0026）或任何时候中枢神经系统复发时间较短在统计学上显著相关的变量（风险比4.3 [95%置信区间1.8至10.3]；p = 0.001）。这些是在非乳腺癌中首次证明HER2阳性与术后中枢神经系统复发风险较高之间存在关联的数据，并表明HER2阳性EAC易发生中枢神经系统转移。
