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Central nervous system relapse in patients with untreated HER2‐positive esophageal or gastroesophageal junction adenocarcinoma
Author(s) -
Yoon Harry H.,
Lewis Mark A.,
Foster Nathan R.,
Sukov William R.,
Khan Maliha,
Sattler Christopher A.,
Wiktor Anne E.,
Wu TsungTeh,
Jenkins Robert B.,
Sinicrope Frank A.
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30200
Subject(s) - medicine , hazard ratio , breast cancer , brain metastasis , oncology , gastroenterology , central nervous system , adenocarcinoma , cancer , confidence interval , esophagus , metastasis , cumulative incidence , incidence (geometry) , cohort , physics , optics
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.