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Univariate logistic regression models for deleterious mutation among 133 sequenced subjects (n = 26 with deleterious mutation).

Univariate Cox proportional hazards model for overall survival among all 233 patients (n deaths=211).

Chemotherapy Response Rate by Mutation Status of Sequenced Cohort (n = 133)

Patient characteristics with statistical comparison between sequenced and unsequenced cohorts among 233 patients.

Multivariable logistic regression model for deleterious mutation among 133 sequenced subjects (n = 26 with deleterious mutation).

Variants of Unknown Significance Identified in Study Cohort

Supplemental Table Legend

Univariate Cox proportional hazards model for overall survival among 133 patients (n deaths = 130).

Purpose: Family history of BRCA-related tumors may correlate with response to chemotherapy and overall survival (OS) in pancreatic cancer. The frequency of germline mutations has been reported in patients predominantly under the age of 60 or with strong family history. We examine the incidence of deleterious germline mutations and compare the chemotherapy responses and OS in an unselected group of patients with metastatic pancreatic cancer. Experimental Design: Patients with metastatic pancreatic cancer, who were seen at a single cancer center between 2010 and 2016, were included. Germline DNA was sequenced using a 263-gene panel to identify novel mutations (N = 133 MD Anderson cohort, N = 127 TCGA cohort). Chemotherapy response and OS were determined by review of medical records. Results: Deleterious germline mutations were identified in 26 of 133 patients (19.5%). Patients with DNA damage repair (DDR) gene mutations (ATM, BRCA1/2, CDKN2A, CHEK2, ERCC4, PALB2, n = 15) had an improved OS as compared with patients without (16.8 vs. 9.1 months, P = 0.03). Conversely, patients with other deleterious mutations had a trend toward worse OS. However, survival in the latter group was longer (P = NS) in those mutants initially treated with gemcitabine/nab-paclitaxel. A family history of multiple breast, ovarian, and pancreatic cancers was associated with DDR gene mutations and better survival. Conclusions: We have identified novel germline mutations that are prognostic for survival in patients with pancreatic cancer. We observe improved survival in patients with DDR gene mutations and worsened survival in patients with deleterious mutations in non-DDR genes.