Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD.
Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD.
J Am Coll Surg. 2018 Apr;226(4):630-637.e1. doi: 10.1016/j.jamcollsurg.2017.12.021. Epub 2018 Jan 5.
The outcomes of sporadic pancreatic ductal adenocarcinoma (PDAC) patients with germline mutations of BRCA1/BRCA2 remains unclear. The prognostic significance of BRCA1/BRCA2 mutations on survival is not well established.
We performed targeted next-generation sequencing (NGS) to identify BRCA1/BRCA2 germline mutations in resected sporadic PDAC cases from 2000 to 2015. Germline BRCA mutation carriers were matched by age and tumor location to those with BRCA1/BRCA2 wild-type genes from our institutional database. Demographics, clinicopathologic features, overall survival (OS), and disease-free survival (DFS) were abstracted from medical records and compared between the 2 cohorts.
Twenty-two patients with sporadic cancer and BRCA1 (n = 4) or BRCA2 (n = 18) germline mutations and 105 wild-type patients were identified for this case-control study. The BRCA1/BRCA2 mutations were associated with inferior median OS (20.2 vs 27.8 months, p = 0.034) and DFS (8.4 vs 16.7 months, p < 0.001) when compared with the matched wild-type controls. On multivariable analyses, a BRCA1/BRCA2 mutation (hazard ratio [HR] 2.10, p < 0.001), positive margin status (HR 1.72, p = 0.021), and lack of adjuvant therapy (HR 2.38, p < 0.001), were all independently associated with worse survival. Within the BRCA1/BRCA2 mutated group, having had platinum-based adjuvant chemotherapy (n = 10) was associated with better survival than alternative chemotherapy (n = 8) or no adjuvant therapy (n = 4) (31.0 vs 17.8 vs 9.3 months, respectively, p < 0.001).
Carriers of BRCA1/BRCA2 mutation with sporadic PDAC had a worse survival after pancreatectomy than their BRCA wild-type counterparts. However, platinum-based chemotherapy regimens were associated with markedly improved survival in patients with BRCA1/BRCA2 mutations, with survival differences no longer appreciated with wild-type patients.
散发性胰腺导管腺癌（PDAC）患者携带 BRCA1/BRCA2 种系突变的预后结果仍不清楚。BRCA1/BRCA2 突变对生存的预后意义尚未得到充分确立。
我们对 2000 年至 2015 年间接受手术的散发性 PDAC 病例进行了靶向二代测序（NGS），以鉴定 BRCA1/BRCA2 种系突变。种系 BRCA 突变携带者按年龄和肿瘤位置与我们机构数据库中 BRCA1/BRCA2 野生型基因的患者相匹配。从病历中提取人口统计学、临床病理特征、总生存期（OS）和无病生存期（DFS），并在两组间进行比较。
这项病例对照研究共纳入 22 例携带散发性癌症和 BRCA1（n=4）或 BRCA2（n=18）种系突变的患者和 105 例野生型患者。与匹配的野生型对照组相比，BRCA1/BRCA2 突变与中位 OS （20.2 与 27.8 个月，p=0.034）和 DFS （8.4 与 16.7 个月，p<0.001）较短相关。多变量分析显示，BRCA1/BRCA2 突变（风险比 [HR] 2.10，p<0.001）、阳性切缘状态（HR 1.72，p=0.021）和缺乏辅助治疗（HR 2.38，p<0.001）均与生存较差独立相关。在 BRCA1/BRCA2 突变组中，接受铂类为基础的辅助化疗（n=10）的患者比接受其他化疗（n=8）或无辅助治疗（n=4）的患者的生存更好（分别为 31.0、17.8 和 9.3 个月，p<0.001）。
携带散发性 PDAC 的 BRCA1/BRCA2 突变患者在接受胰腺切除术后面临更差的生存。然而，铂类为基础的化疗方案与 BRCA1/BRCA2 突变患者的显著生存改善相关，与野生型患者相比，生存差异不再明显。
