Unusual dMMR Phenotype Locally Advanced Pancreatic Ductal Adenocarcinoma with Germline and Somatic BRCA2 Mutation in a Jehovah Witness Patient

Abstract

• •

  PDAC is a genetically heterogenous disease with various molecular subtypes which may explain variations in treatment response. Genetic mutations and altered molecular pathways serve as targets in therapy and may improve outcomes.

• •

  Neoadjuvant systemic therapy with or without radiation followed by evaluation for surgery is an accepted treatment approach for locally advanced disease with the goal of enabling an R0 resection to achieve improved disease-free and overall survival.

• •

  In many cancers, including pancreatic cancer, MSI is a predictive biomarker for response to immunotherapy, and a prognostic factor for survival. Treatment with neoadjuvant chemoimmunotherapy in this group of patients usually leads to pathologic complete responses.

• •

  Although rare (15%), an unusual dMMR phenotype, evidenced by discordance between IHC staining of MMR proteins and next gen sequencing, do exist. In this group of patients available data show varying responses to immunotherapy ranging from complete, to partial responses to stable disease.

• •

  We present successful treatment outcome in a locally advanced PDAC case with dMMR and germline plus somatic BRCA2 mutation treated with available chemotherapy immunotherapy and targeted therapy options.