We here report a case of a patient diagnosed with human epithelial
growth factor receptor 2 (HER2)-amplified esophageal
adenocarcinoma. The patient responded well to
trastuzumab-based
chemotherapy initially, but progressed with liver
metastases. Her treatment was then switched to dual HER2 blockade with both
trastuzumab and
lapatinib in combination with
capecitabine. She tolerated
therapy and responded remarkably well with radiographic resolution of liver
metastases. Unfortunately, she developed multiple
brain metastases in the absence of extracranial progression. Discordant negative expression of HER2 and subclonal mutations in brain lesions were discovered, which, at least in part, explained her
brain metastases in the presence of
capecitabine and
lapatinib, as both agents are known to be able to cross the blood brain barrier. The potential mechanism for dual HER2 blockade is discussed in the context of HER2-positive,
trastuzumab-resistant, advanced
esophageal cancer. The incidence of brain
metastasis in advanced gastro-
esophageal cancer has been reported to be extremely low, but is expected to increase with more effective systemic
therapy. The intratumoral heterogeneity between the
metastases, local recurrences and the primary
tumor is definitely noteworthy.