Clinical significance of germline breast cancer susceptibility gene (gBRCA) testing and olaparib as maintenance therapy for patients with pancreatic cancer.

Background: Germline breast cancer susceptibility gene (gBRCA) mutation in patients with pancreatic cancer (PC) is not common in clinical practice. Therefore, factors that efficiently show gBRCA mutations and the real-world outcomes of olaparib maintenance therapy have not been fully established. In the present study, we clarified the indicators for the effective detection of gBRCA mutation and the efficacy and safety of olaparib as maintenance therapy.

Methods: We retrospectively analyzed 84 patients with PC who underwent gBRCA testing (BRACAnalysis, Myriad Genetics, Salt Lake City, UT, USA) at our institute between January 2021 and March 2022. For each patient, clinical data were extracted from medical records.

Results: The median patient age was 64 y (29-85 y), and 41 patients (48.8%) were male. The gBRCA mutations were identified in 10 (11.9%) patients; two patients had BRCA1 mutation and eight had BRCA2 mutation. All patients with gBRCA mutation had a family history of any cancer, and eight of them had a family history of Hereditary Breast and Ovarian Cancer syndrome (HBOC)-related cancer. The gBRCA mutation rate was higher for patients with PC with a family history of HBOC-related cancer compared to that in patients with PC having a family history of other cancers and no family history of cancer (22.9% vs. 4.1%; P = 0.014). In our study, eight out of 10 patients with gBRCA-positive PC received olaparib after platinum-based chemotherapy. The best responses to platinum-based chemotherapy included a complete response in one patient (12.5%) and a partial response in seven patients (87.5%). The median duration of treatment with platinum-based chemotherapy plus olaparib was 17.5 months (8-87 months), and the duration of treatment with olaparib maintenance therapy was 11 months (1-30 months). During olaparib maintenance therapy, three patients showed no disease progression. One of these three patients underwent conversion surgery after receiving olaparib for 12 months.

Conclusions: The gBRCA testing should be considered proactively, especially in patients with PC with a family history of HBOC-related cancer.