Introduction: Pancreatic adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. While germline mutations in BRCA1/2 are well-established risk factors, mutations in the BLM gene (associated with Bloom Syndrome) are rare in this context.
Case presentation: We present a 73-year-old female with a recent history of small cell lung cancer (SCLC) who presented with metastatic pancreatic adenocarcinoma. Genetic profiling revealed a pathogenic germline BLM mutation and a somatic ATM mutation. The patient was treated with an oxaliplatin-based regimen (mFOLFOX6), modified due to comorbidities, achieving disease stabilization.
Discussion: This case highlights the complexity of managing metachronous malignancies and the utility of comprehensive genomic profiling. The presence of pathogenic variants in DNA damage response (DDR) genes (BLM and ATM) suggests a defect in homologous recombination, providing a rationale for platinum-based therapy. We discuss the implications of BLM mutations on therapeutic selection, potential immune checkpoint interactions, and the role of synthetic lethality in management.
Keywords: BLM Mutations; Hyperlipidemia; Metachronous Malignancies; Pancreatic Adenocarcinoma; Small Cell Lung Cancer.