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Pancreatic Cancer BRCA — SCE Medical Oncology MCQ

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HardGI CancersPancreatic Cancer BRCASCE Medical Oncology

A 60-year-old woman with metastatic pancreatic cancer and a family history of breast cancer is offered somatic tumour profiling. Results show a somatic BRCA2 mutation (not germline). She has progressed on FOLFIRINOX. What is the potential treatment implication?

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Correct answer: B — Somatic BRCA2 mutation may predict sensitivity to platinum-based chemotherapy and PARP inhibitors (olaparib)

The POLO trial demonstrated that olaparib maintenance improved PFS compared with placebo in metastatic pancreatic cancer with germline BRCA1/2 mutations after platinum-based chemotherapy. Emerging evidence suggests that somatic BRCA mutations may also confer PARP inhibitor sensitivity, as the underlying DNA repair deficiency is functionally similar. Additionally, the presence of any BRCA mutation (somatic or germline) confirms prior platinum sensitivity may be related to HRD. Germline testing should also be recommended given the family history.

Reference: ESMO 2024 Pancreatic Cancer Guidelines; POLO Golan et al NEJM 2019