{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T05:43:02Z","timestamp":1775194982177,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,6,10]],"date-time":"2016-06-10T00:00:00Z","timestamp":1465516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004676","name":"CA Technologies","doi-asserted-by":"publisher","award":["114740"],"award-info":[{"award-number":["114740"]}],"id":[{"id":"10.13039\/100004676","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:p>Although HER2\u2010positive breast cancers demonstrate a propensity for central nervous system (CNS) metastasis, it is unknown whether other HER2\u2010positive tumors, including adenocarcinomas of the esophagus\/gastroesophageal junction (EAC), share this characteristic. Insight into this association may inform the development of HER2\u2010targeted therapies that penetrate the blood\u2010brain barrier. We examined HER2 overexpression and gene amplification in 708 patients with EAC who underwent curative\u2010intent surgery during a time period (1980\u20131997) when no patient received HER2\u2010targeted 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\u2010up of 61.2 months, 3.4% (24\/708) of patients developed CNS relapse (all involved the brain). Patients with HER2\u2010positive (<jats:italic>vs<\/jats:italic> \u2010negative) primary tumors showed a higher 5\u2010year cumulative incidence of CNS relapse as first recurrence (5.8% <jats:italic>vs<\/jats:italic>. 1.2%; <jats:italic>p<\/jats:italic>\u2009=\u20090.0058) and at any time (8.3% <jats:italic>vs<\/jats:italic>. 2.4%; <jats:italic>p<\/jats:italic>\u2009=\u20090.0062). 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 (<jats:italic>p<\/jats:italic>\u2009=\u20090.0026) or at any time (hazard ratio 4.3 [95% confidence interval 1.8 to 10.3]; <jats:italic>p<\/jats:italic>\u2009=\u20090.001). These are the first data in a non\u2010breast cancer to demonstrate an association between HER2 positivity and higher CNS relapse risk after surgery, and suggest that HER2\u2010positive EACs have a predilection for CNS metastases.<\/jats:p>","DOI":"10.1002\/ijc.30200","type":"journal-article","created":{"date-parts":[[2016,5,21]],"date-time":"2016-05-21T15:22:37Z","timestamp":1463844157000},"page":"1626-1631","source":"Crossref","is-referenced-by-count":18,"title":["Central nervous system relapse in patients with untreated HER2\u2010positive esophageal or gastroesophageal junction adenocarcinoma"],"prefix":"10.1002","volume":"139","author":[{"given":"Harry H.","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Mayo Clinic Rochester MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology MD Anderson Cancer Center Houston 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