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Background  Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Repurposing of therapeutics that target specific molecular mechanisms in different disease types offers potential for rapid improvements in outcome. Although  HER2  amplification occurs in pancreatic cancer, it is inadequately characterized to 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) with pancreatic ductal adenocarcinoma (PDAC).    Results  An amplified inversion event (1 MB) was identified at the  HER2  locus in a patient with PDAC. Using standardized laboratory assays, we established diagnostic criteria for  HER2  amplification in PDAC, and observed a prevalence of 2%. Clinically,  HER2 - amplified PDAC was characterized by a lack of liver metastases, and a preponderance of lung and brain metastases. Excluding breast and gastric cancer, the incidence of  HER2 -amplified cancers in the USA is >22,000 per annum.    Conclusions   HER2  amplification occurs in 2% of PDAC, and has distinct features with implications for clinical practice. The molecular heterogeneity of PDAC implies that even an incidence of 2% represents an attractive target for anti- HER2  therapies, as options for PDAC are limited. Recruiting patients based on  HER2  amplification, rather than organ of origin, could make trials of anti-HER2 therapies feasible in less common cancer types.

Clinical and molecular characterization of HER2 amplified-pancreatic cancer