clinical and molecular characterization of her2 amplified-pancreatic cancer

background: pancreatic cancer is one of the most lethal and molecularly diverse malignancies. repurposing oftherapeutics that target specific molecular mechanisms in different disease types offers potential for rapidimprovements in outcome. although her2 amplification occurs in pancreatic cancer, it is inadequately characterizedto exploit the potential of anti-her2 therapies. methods: her2 amplification was detected and further analyzed using multiple genomic sequencing approaches.standardized reference laboratory assays defined her2 amplification in a large cohort of patients (n = 469) withpancreatic ductal adenocarcinoma (pdac). results: an amplified inversion event (1 mb) was identified at the her2 locus in a patient with pdac. usingstandardized laboratory assays, we established diagnostic criteria for her2 amplification in pdac, and observed aprevalence of 2%. clinically, her2- amplified pdac was characterized by a lack of liver metastases, and apreponderance of lung and brain metastases. excluding breast and gastric cancer, the incidence of her2-amplifiedcancers in the usa is >22,000 per annum. conclusions: her2 amplification occurs in 2% of pdac, and has distinct features with implications for clinicalpractice. the molecular heterogeneity of pdac implies that even an incidence of 2% represents an attractive targetfor anti-her2 therapies, as options for pdac are limited. recruiting patients based on her2 amplification, ratherthan organ of origin, could make trials of anti-her2 therapies feasible in less common cancer types.