Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chou-ku, Osaka, 541-8567, Japan.
Department of Gastroenterology, Osaka General Medical Center, Osaka, Japan.
BMC Cancer. 2024 Aug 12;24(1):1000. doi: 10.1186/s12885-024-12722-8.
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.
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.
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.
The gBRCA testing should be considered proactively, especially in patients with PC with a family history of HBOC-related cancer.
在临床实践中，胰腺癌（PC）患者的种系乳腺癌易感基因（gBRCA）突变并不常见。因此，尚未充分明确能够有效显示 gBRCA 突变的因素以及奥拉帕利维持治疗的真实世界结局。本研究旨在阐明有效检测 gBRCA 突变的指标以及奥拉帕利作为维持治疗的疗效和安全性。
我们回顾性分析了 2021 年 1 月至 2022 年 3 月在我院接受 gBRCA 检测（BRACAnalysis，Myriad Genetics，盐湖城，UT，美国）的 84 例 PC 患者的临床资料。从病历中提取每位患者的临床资料。
患者中位年龄为 64 岁（29-85 岁），41 例（48.8%）为男性。10 例（11.9%）患者存在 gBRCA 突变；2 例存在 BRCA1 突变，8 例存在 BRCA2 突变。所有存在 gBRCA 突变的患者均有癌症家族史，其中 8 例有遗传性乳腺癌和卵巢癌综合征（HBOC）相关癌症家族史。存在 HBOC 相关癌症家族史的 PC 患者 gBRCA 突变率高于存在其他癌症家族史和无癌症家族史的 PC 患者（22.9% vs. 4.1%；P=0.014）。在本研究中，10 例 gBRCA 阳性 PC 患者中有 8 例在铂类化疗后接受了奥拉帕利治疗。铂类化疗的最佳反应包括 1 例患者（12.5%）完全缓解和 7 例患者（87.5%）部分缓解。铂类化疗联合奥拉帕利治疗的中位时间为 17.5 个月（8-87 个月），奥拉帕利维持治疗的时间为 11 个月（1-30 个月）。在奥拉帕利维持治疗期间，3 例患者无疾病进展。这 3 例患者中有 1 例在接受奥拉帕利治疗 12 个月后进行了转化手术。
应积极考虑进行 gBRCA 检测，特别是在有 HBOC 相关癌症家族史的 PC 患者中。
