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携带BRCA突变的I/II期胰腺癌患者的总生存期及临床特征

Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer.

作者信息

Golan Talia, Sella Tal, O'Reilly Eileen M, Katz Matthew H G, Epelbaum Ron, Kelsen David P, Borgida Ayelet, Maynard Hannah, Kindler Hedy, Friedmen Eitan, Javle Milind, Gallinger Steven

机构信息

Department of Oncology, Sheba Medical Center, Ramat Gan 52621, Israel.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.

出版信息

Br J Cancer. 2017 Mar 14;116(6):697-702. doi: 10.1038/bjc.2017.19. Epub 2017 Feb 9.

Abstract

BACKGROUND

BRCA1/BRCA2 germ line (GL) mutation carriers with pancreatic adenocarcinoma (PDAC) may have distinct outcomes. We recently described an apparent more favourable prognosis of surgically resected BRCA-associated PDAC patients in a single-arm, uncontrolled, retrospective study. However, the prognostic impact of GL BRCA1/2 mutations in surgically resected PDAC has not been compared with a matched control population.

METHODS

A larger multi-centre, case-control retrospective analysis was performed. Cases were patients with surgically resected, BRCA1/2-associated PDAC from 2004 to 2013. Controls included surgically resected PDAC cases treated during the same time period that were either BRCA non-carriers, or had no family history of breast, ovarian or pancreatic cancers. Cases and controls were matched by: age at diagnosis (within ±5-year period) and institution. Demographics, clinical history, overall survival (OS) and disease-free survival (DFS) were abstracted from patient records. Statistical comparisons were assessed using χ- and Fisher's exact test, and median DFS/OS using Kaplan-Meier method and log-rank testing.

RESULTS

Twenty-five patients with BRCA1-(n=4) or BRCA2 (N=21)-associated resectable PDAC were identified. Mean age was 55.7 years (range, 34-78 years), 48% (n=12) were females and 76% (n=19) were Jewish. Cases were compared (1 : 2) with 49 resectable PDAC controls, and were balanced for age, ethnicity and other relevant clinical and pathological features. BRCA-associated PDAC patients received neoadjuvant, or adjuvant platinum-based treatment more frequently than controls (7 out of 8 vs 6 out of 14) and (7 out of 21 vs 3 out of 44), respectively. No significant difference in median OS (37.06 vs 38.77 months, P=0.838) and in DFS (14.3 vs 12.0 months, P=0.303) could be demonstrated between cases and controls. A trend to increased DFS was observed among BRCA-positive cases treated with neoadjuvant/adjuvant platinum-containing regimens (n=10) compared with similarly treated controls (n=7) (39.1 vs 12.4 months, P=0.255).

CONCLUSIONS

In this retrospective analysis, the prognosis of surgically resectable BRCA-associated PDAC is no different than that of sporadic PDAC from the same institution. The role of platinum-based adjuvant therapy in this setting requires prospective investigation.

摘要

背景

携带BRCA1/BRCA2种系(GL)突变的胰腺腺癌(PDAC)患者可能有不同的预后。我们最近在一项单臂、非对照、回顾性研究中描述了手术切除的BRCA相关PDAC患者明显更有利的预后。然而,GL BRCA1/2突变对手术切除的PDAC患者的预后影响尚未与匹配的对照人群进行比较。

方法

进行了一项更大规模的多中心病例对照回顾性分析。病例为2004年至2013年手术切除的BRCA1/2相关PDAC患者。对照包括同期接受手术切除的PDAC病例,这些病例要么是非BRCA携带者,要么没有乳腺癌、卵巢癌或胰腺癌家族史。病例和对照按以下因素匹配:诊断时的年龄(在±5年范围内)和机构。从患者记录中提取人口统计学、临床病史、总生存期(OS)和无病生存期(DFS)。使用χ检验和Fisher精确检验进行统计比较,使用Kaplan-Meier方法和对数秩检验评估中位DFS/OS。

结果

确定了25例携带BRCA1(n = 4)或BRCA2(n = 21)相关可切除PDAC的患者。平均年龄为55.7岁(范围34 - 78岁),48%(n = 12)为女性,76%(n = 19)为犹太人。将病例(1∶2)与49例可切除PDAC对照进行比较,在年龄、种族以及其他相关临床和病理特征方面达到平衡。BRCA相关PDAC患者接受新辅助或辅助铂类治疗的频率高于对照组,分别为8例中的7例对14例中的6例以及21例中的7例对44例中的3例。病例组和对照组之间在中位OS(37.06对38.77个月,P = 0.838)和DFS(14.3对12.0个月,P = 0.303)方面无显著差异。与接受类似治疗的对照组(n = 7)相比,接受新辅助/辅助含铂方案治疗的BRCA阳性病例(n = 10)中观察到DFS有增加趋势(39.1对12.4个月,P = 0.255)。

结论

在这项回顾性分析中,手术可切除的BRCA相关PDAC的预后与同一机构的散发性PDAC无异。铂类辅助治疗在此情况下的作用需要前瞻性研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ccb/5355924/be0a910fbe5c/bjc201719f1.jpg

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