Exceptional Response of Pancreatic Acinar Cell Carcinoma and Bile Duct Cancer to Platinum-Based Chemotherapy in a Family With a Germline BRCA2 Variant

Abstract Pancreatic cancer and its rare subtype, acinar cell carcinoma (PACC), frequently harbor germline and/or somatic variants in homologous recombinant genes, including BRCA2 . Individuals possessing germline pathogenic BRCA2 variants are known to have a higher risk of developing various cancers, including breast, ovarian, pancreatic, and bile duct cancers (BDCs). It has been reported that tumors positive for BRCA1 / 2 variants are sensitive to platinum-based agents. Thus, BRCA1 / 2 germline testing and comprehensive genomic profiling are recommended to identify genetic susceptibility and to indicate optimal targeted therapy. Here, we report familial occurrence of PACC and BDC associated with BRCA2 ; both tumors responded exceptionally well to platinum-based chemotherapy. A 37-year-old man was diagnosed with unresectable PACC with a germline BRCA2 variant. He was treated with oxaliplatin-containing chemotherapy and conversion surgery, and remains alive without tumor recurrence after more than 36 months. His father also possessed the identical germline BRCA2 variant and was diagnosed with extrahepatic BDC with lymph node metastases. The tumors showed marked shrinkage upon treatment with cisplatin-containing chemotherapy. Our cases underscore the importance of comprehensive genomic profiling and genetic testing for BRCA2 to ensure optimal therapeutic options for PACC as well as to identify high-risk individuals with various cancers in the family.