Concurrent EGFR exon 19 deletion-insertion and germline BRCA1 alteration in KRAS-wild-type pancreatic ductal adenocarcinoma: A case report and review of therapeutic implications.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies, with a dismal prognosis and a 5-year overall survival rate of 5-10%. Owing to the absence of specific symptoms at early stages, the majority of patients are first diagnosed with already locally advanced or metastatic disease. Consequently, such patients are ineligible for curative surgery, resulting in limited therapeutic options and poor outcomes. With advances in molecular profiling and next-generation sequencing, precision medicine has emerged as an important therapeutic approach for advanced PDAC. Targeted therapies directed against specific molecular alterations, including BRCA1/2, HER2 and KRAS, have demonstrated clinical benefit in selected patient populations. However, current evidence predominantly focuses on single gene alterations. There is a lack of data and consensus regarding the optimal treatment strategies for PDAC harboring concurrent multiple genomic aberrations. In the present report, a rare case of KRAS wild-type PDAC harboring a somatic EGFR exon 19 deletion-insertion mutation, a heterozygous germline BRCA1 splice-site mutation and an additional somatic synonymous TP53 variant identified by molecular testing was documented. The patient developed clinically suspected postoperative recurrence and subsequently achieved durable disease control following individualized exploratory treatment with aumolertinib and olaparib. The present case provides a clinically documented observation of individualized targeted therapy in a rare KRAS wild-type PDAC molecular context and may help inform future hypothesis-driven investigations in selected molecularly defined patients. However, further studies are required to clarify the functional relevance of these molecular alterations and the clinical value of this treatment approach in selected patients with molecularly unique PDAC.