Clinical Study

British Journal of Cancer (2017) 116, 697–702. doi:10.1038/bjc.2017.19 www.bjcancer.com
Published online 9 February 2017

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

Talia Golan1,2,13, Tal Sella1,2,13,14, Eileen M O'Reilly3,4, Matthew H G Katz5, Ron Epelbaum6,7, David P Kelsen3,4, Ayelet Borgida8, Hannah Maynard3,4, Hedy Kindler9, Eitan Friedmen2,10, Milind Javle11 and Steven Gallinger8,12

  1. 1Department of Oncology, Sheba Medical Center, Ramat Gan 52621, Israel
  2. 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
  3. 3Department of Medicine, Memorial Sloan Kettering Cancer Center New York, New York, NY 10065, USA
  4. 4Weill Cornell Medical College New York, New York, NY 10065, USA
  5. 5Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
  6. 6Department of Oncology, Rambam Health Care Campus, Haifa 3109601, Israel
  7. 7The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel
  8. 8Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
  9. 9Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA
  10. 10The Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Ramat Gan 52621, Israel
  11. 11Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
  12. 12Department of Surgery, University Health Network, Toronto, ON M5G 2C4, Canada

Correspondence: Dr T Golan, E-mail: Talia.Golan@sheba.health.gov.il

13These authors contributed equally to this work.

14Dr Pinchas Borenstein Talpiot Medical Leadership Program.

Received 6 June 2016; Revised 25 December 2016; Accepted 10 January 2017
Advance online publication 9 February 2017

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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 χ2- 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.

Keywords:

BRCA 1; BRCA2; pancreatic cancer; OS; case–control study; DFS