title: Central nervous system relapse in patients with untreated HER2-positive esophageal or gastroesophageal junction adenocarcinoma.
abstract: 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.
authors.affiliation: Department of Medical Oncology, Mayo Clinic, Rochester, MN.
authors.forename: Harry H
authors.initials: HH
authors.lastname: Yoon
authors.affiliation: Department of Medical Oncology, MD Anderson Cancer Center, Houston, TX.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lewis
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Foster
authors.affiliation: Department of Cytogenetics, Mayo Clinic, Rochester, MN.
authors.forename: William R
authors.initials: WR
authors.lastname: Sukov
authors.affiliation: Department of Leukemia Department, MD Anderson Cancer Center, Houston, TX.
authors.forename: Maliha
authors.initials: M
authors.lastname: Khan
authors.affiliation: Department of Cytogenetics, Mayo Clinic, Rochester, MN.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Sattler
authors.affiliation: Mayo Collaborative Services, Mayo Clinic, Rochester, MN.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Wiktor
authors.affiliation: Anatomic Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Tsung-Teh
authors.initials: TT
authors.lastname: Wu
authors.affiliation: Department of Cytogenetics, Mayo Clinic, Rochester, MN.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.affiliation: Department of Medical Oncology, Mayo Clinic, Rochester, MN.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Sinicrope
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004943:Esophagogastric Junction / Q000201:enzymology / Q000473:pathology*; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: CNS; HER2/ERBB2; brain; gastroesophageal cancer; relapse