Background Patients with DNA-damage response genes (DDR)-related pancreas cancer ( BRCA1/2 or other DNA-damage related genes) may have improved outcomes secondary to increased sensitivity to DNA-damaging drugs (platinum chemotherapy/ poly ADP ribose polymerase (PARP)-inhibitors). However, data is scarce pertaining to outcomes in this subset of patients. Our objective was to retrospectively identify DDR-related pancreas cancer patients and report on clinical outcomes. Methods Pancreas cancer patients with a germline pathogenic variant in BRCA1/2 or other DDR gene were identified retrospectively through review of medical records (medical genetics/oncology) and genetic testing results at our institution. Data regarding clinical outcomes, therapy received, and survival was subsequently extracted. Results A total of 11 patients with pancreas cancer were identified to carry a pathogenic DDR-variant: BRCA1 (3), ATM (4), BRCA2 (2), PALB2 (1) and FANCC (1). Five of these individuals had prior history of other cancers. Clinically these tumors were localized (4), locally advanced (3), and metastatic (4) at diagnosis. Four out of 11 patients were still alive at time of data review. Survival in the 7 patients who had died was 13.7, 140.0, 20.5, 22.3, 23.5, 25.8, and 111.5 months. All patients with advanced disease had exposure to platinum chemotherapy. Conclusions Historical survival in patients with advanced and metastatic pancreas cancer is poor. Results of this DDR-subset of patients do show significantly superior outcomes, likely secondary to exposure to platinum drugs. This data, alongside other similar cohorts, would favor the DDR-genes being a predictive marker with improved survival if exposed to these drugs and the new class of drugs, PARP-inhibitors.

中文翻译：

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DNA 损伤修复相关胰腺癌患者结局的回顾性评价

背景 患有 DNA 损伤反应基因 (DDR) 相关胰腺癌（BRCA1/2 或其他 DNA 损伤相关基因）的患者可能会因对 DNA 损伤药物（铂类化疗/聚 ADP 核糖聚合酶 (PARP) 的敏感性增加）而改善预后。 )-抑制剂)。然而，关于这部分患者的结果的数据很少。我们的目标是回顾性识别 DDR 相关的胰腺癌患者并报告临床结果。方法通过查阅我院病历（医学遗传学/肿瘤学）和基因检测结果，回顾性鉴定出携带 BRCA1/2 或其他 DDR 基因种系致病性变异的胰腺癌患者。随后提取有关临床结果、接受的治疗和生存的数据。结果 共有 11 名胰腺癌患者被鉴定携带致病性 DDR 变异：BRCA1 (3)、ATM (4)、BRCA2 (2)、PALB2 (1) 和 FANCC (1)。其中五人有其他癌症病史。临床上，这些肿瘤在诊断时为局限性 (4)、局部晚期 (3) 和转移性 (4)。在数据审查时，11 名患者中有 4 名仍然活着。7 名死亡患者的生存期分别为 13.7、140.0、20.5、22.3、23.5、25.8 和 111.5 个月。所有晚期疾病患者均接受过铂类化疗。结论 晚期和转移性胰腺癌患者的历史生存率很差。该 DDR 患者子集的结果确实显示出明显优越的结果，可能是继发于铂类药物的暴露。该数据与其他类似的队列一起，有利于 DDR 基因作为预测标记，如果暴露于这些药物和新型药物 PARP 抑制剂，可以提高生存率。