Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer.
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.
Department of Oncology, Sheba Medical Center, Ramat Gan 52621, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
Talia
T
Golan
Department of Oncology, Sheba Medical Center, Ramat Gan 52621, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
Tal
T
Sella
Department of Medicine, Memorial Sloan Kettering Cancer Center New York, New York, NY 10065, USA.|Weill Cornell Medical College New York, New York, NY 10065, USA.
Eileen M
EM
O'Reilly
Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Matthew H G
MH
Katz
Department of Oncology, Rambam Health Care Campus, Haifa 3109601, Israel.|The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel.
Ron
R
Epelbaum
Department of Medicine, Memorial Sloan Kettering Cancer Center New York, New York, NY 10065, USA.|Weill Cornell Medical College New York, New York, NY 10065, USA.
David P
DP
Kelsen
Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
Ayelet
A
Borgida
Department of Medicine, Memorial Sloan Kettering Cancer Center New York, New York, NY 10065, USA.|Weill Cornell Medical College New York, New York, NY 10065, USA.
Hannah
H
Maynard
Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA.
Hedy
H
Kindler
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.|The Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Ramat Gan 52621, Israel.
Eitan
E
Friedmen
Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Milind
M
Javle
Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
Steven
S
Gallinger
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D018095:Germ-Line Mutation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human