Case Presentation: BRCA2-Directed Therapy in Metastatic Pancreatic Cancer Case Presentation
Patient Case:
A 63-year-old woman with a past medical history of breast cancer and a strong family history of breast and ovarian cancer presents with unintentional weight loss, jaundice (total bilirubin 9.6), and epigastric pain. CT imaging reveals a pancreatic head mass causing biliary obstruction, along with multifocal liver lesions. During an ERCP/EUS, a biliary stent is placed, and biopsy results are "suspicious for adenocarcinoma." A liver biopsy later confirms a moderately differentiated adenocarcinoma. Immunohistochemistry is positive for CK7 and CK19, and negative for TTF1. Her ECOG performance status is 1.
Given her personal history of breast cancer and family history of breast and ovarian cancer, the patient underwent germline genetic testing, which revealed a germline BRCA2 c.6174delT alteration. Tumor-based NGS profiling also identified the BRCA2 c.6174delT mutation, accompanied by a single-copy deletion of BRCA2, indicative of biallelic loss. Additionally, NGS profiling revealed a KRAS G12D mutation and a two-copy deletion of both CDKN2A and MTAP.
The patient was initiated on FOLFIRINOX chemotherapy. Although the side effects were challenging, restaging scans after 4 and 8 cycles showed a marked reduction in tumor burden (approximately 52% by RECIST criteria). After 8 cycles, the patient experienced intolerable toxicity, particularly neuropathy and fatigue, and requested a chemotherapy holiday.
Given the excellent response to FOLFIRINOX and the biallelic loss of BRCA2, the patient was transitioned to olaparib maintenance therapy. Her tumor continued to respond well to treatment, and remarkably, she has maintained a durable response, remaining on olaparib after 3 years of treatment.
