- A review calls for more frequent testing of germline mutations in patients with pancreatic ductal adenocarcinoma (PDAC), as well as more research to identify therapeutic targets.
Why this matters
- Almost 1 in 10 patients with PDAC has an actionable germline mutation.
- Several recent data sets have shown evidence of pathogenic germline alterations (PGAs), at a frequency of about 10%.
- Most common are BRCA1, BRCA2, and ATM.
- Least common include PALB2, MLH1, MSH2, MSH6, PMS2, CDKN2A, and TP53.
- Aggregate frequencies range from 3.8% to 9.7%.
- BRCA1/2 mutations identified in 3%-7% of patients with PDAC.
- The American Society of Clinical Oncology and the National Comprehensive Cancer Network now recommend assessing all patients with PDAC for PGAs, even without a family history or ethnic factors.
- Treatment options influenced by PGAs include:
- Checkpoint inhibitor therapy for mismatch repair-deficient and microsatellite instability PDAC.
- Poly-ADP (adenosine diphosphate)-ribose polymerase (i.e., PARP) inhibitor therapy as a maintenance approach and platinum therapy for BRCA1/2 and PALB2 PDAC.