HER2-Positive Gastroesophageal Cancers Are Associated with a Higher Risk of Brain Metastasis

SIMPLE SUMMARY: For patients who develop brain metastasis, the consequences can be devastating, with neurological complications and potentially rapid death. Early intervention with surgery and radiotherapy can prevent neurological complications and improve patient survival. Gastroesophageal cancers which express human epidermal growth factor 2 (HER2) behave differently to those lacking expression. We aimed to review patients who developed brain metastasis from gastroesophageal cancers and assess the risk of HER2 expression on developing brain metastasis. A total of 12 patients developed brain metastasis from the 201 assessed with metastatic gastroesophageal cancer. The life expectancy of patients with gastroesophageal cancer was similar regardless of HER2 expression. However, the risk of developing brain metastasis was significantly increased. Clinicians need to have a low threshold for investigation of neurological symptoms in patients with HER2-positive gastroesophageal adenocarcinoma. The assessment of current HER2-targeted treatments, and development of new drugs is needed in this under researched area of gastroesophageal cancers. ABSTRACT: Brain metastasis from gastroesophageal adenocarcinomas (GOCs) is a rare but a devastating diagnosis. Human epidermal growth factor receptor 2 (HER2) is a prognostic and predictive biomarker in GOCs. The association of HER2 with GOC brain metastasis is not known. We performed a retrospective analysis of patients with GOCs with known HER2 status between January 2015 and November 2021. HER2 was assessed on either the primary tumour or metastasis by immunohistochemistry or in situ hybridization. The diagnosis of brain metastasis was made on standard imaging techniques in patients with symptoms or signs. HER2 results were available for 201 patients, with 34 patients (16.9%) HER2 positive. A total of 12 patients developed symptomatic brain metastasis from GOCs, of which 7 (58.3%) were HER2 positive. The development of symptomatic brain metastasis was significantly higher in the HER2-positive GOCs (OR8.26, 95%CI 2.09–35.60; p = 0.0009). There was no significant association of HER2 status and overall survival in patients with brain metastasis. Although the rate of brain metastasis remains low in GOCs, the incidence of symptomatic brain metastasis was significantly higher in patients with HER2-positive tumours.