Central nervous system relapse in patients with untreated HER2-positive esophageal or gastroesophageal junction adenocarcinoma

Harry H Yoon, Mark A. Lewis, Nathan R. Foster, William R. Sukov, Maliha Khan, Christopher A. Sattler, Anne E. Wiktor, Tsung Teh Wu, Robert Brian Jenkins, Frank A Sinicrope

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1626-1631
Number of pages6
JournalInternational Journal of Cancer
Volume139
Issue number7
DOIs
StatePublished - Oct 1 2016

Fingerprint

Esophagogastric Junction
Adenocarcinoma
Central Nervous System
Recurrence
Neoplasms
Breast Neoplasms
Neoplasm Metastasis
erbB-2 Genes
Gene Amplification
Blood-Brain Barrier
Confidence Intervals

Keywords

  • brain
  • CNS
  • gastroesophageal cancer
  • HER2/ERBB2
  • relapse

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Central nervous system relapse in patients with untreated HER2-positive esophageal or gastroesophageal junction adenocarcinoma. / 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 Brian; Sinicrope, Frank A.

In: International Journal of Cancer, Vol. 139, No. 7, 01.10.2016, p. 1626-1631.

Research output: Contribution to journalArticle

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 Brian ; Sinicrope, Frank A. / Central nervous system relapse in patients with untreated HER2-positive esophageal or gastroesophageal junction adenocarcinoma. In: International Journal of Cancer. 2016 ; Vol. 139, No. 7. pp. 1626-1631.
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