HER2 positivity in brain metastases from gastrointestinal primary malignancies.

Abstract

61 Background: HER2 amplification in gastrointestinal (GI) cancers, beyond gastric cancer, is uncommon and as a result infrequently tested. In breast cancer, HER2 amplification has been associated with brain metastases (BM) with associated prognostic value and therapeutic opportunity. The purpose of this project was to determine if HER2 amplification is more frequent in GI cancer patients with brain metastases. Methods: Retrospective review of our institution’s medical record system identified all patients with GI primary malignancies who had resection of BM between 1999-2015 with tissue available. Fluorescence in-situ hybridization for HER2 amplification and immunohistochemistry for HER2 expression was performed on each sample and quantified by a board-certified pathologist. Results: Twenty-five GI cancer patients with BM were identified: 40% esophageal adenocarcinoma (AC), 12% esophageal squamous cell carcinoma (SCC), 44% colorectal AC and 4% pancreatic AC. At diagnosis 36% had metastatic disease. A BM was the isolated first site of metastasis in: 11/13 esophageal cancers, 1/11 colorectal cancers and 1/1 pancreatic cancer. Two esophageal cancer patients and one colon cancer patient had BM at diagnosis but otherwise median time to BM was 30 months (range 4-127 months). There was a median of 1 BM with a maximum of 4 lesions per patient. The most common intracranial site was the cerebellum (40%) with a median metastasis size of 27 mm (range 5-55 mm). Overall, HER2 was amplified in 24% (n=6) with 4 of these patients having paired primary tumor tissue available. None of the primary tumor tissue was HER2 amplified. No colorectal cancer patients had HER2 amplification but 67% of esophageal SCC, 30% of esophageal AC and the only pancreatic AC patient had Her2 amplified and overexpressed brain metastases. Conclusions: HER2 amplification was enriched in esophageal SCC and AC patients who developed resectable BM despite none of these patients having HER2 amplification in their primary tissue. HER2 amplification testing in esophageal cancer patients with BM (regardless of histology) may lead to additional therapeutic options, even if primary tissue was negative for HER2 amplification.