Changing the landscape of germline testing in patients with pancreatic adenocarcinoma.

Abstract

676 Background: Results from the POLO trial demonstrated the benefits of PARP inhibition in patients (pts) with germline BRCA-mutated metastatic pancreatic cancer (PC). In 2018, ASCO and NCCN updated their guidelines to recommend that pts with a personal history of PC undergo germline testing. We examined referral patterns and frequency of germline pathogenic variants in pts with PC. Methods: A retrospective review was performed of PC pts seen at the Levine Cancer Institute (LCI) Center for Genetics between January 2010 and September 2019. Descriptive analyses were completed on demographics and appointment outcomes. Results: A total of 201 PC pts were referred; 20 canceled and 14 no-showed their appointment. The remaining 167 were seen and included in this analysis. Most pts (59%) were referred after July 2018. The median age was 65 years (range 32-90) and 19% were < 50 years. The majority of pts were female (61%). Race was most often reported as white (72%) followed by black (20%). Reported family histories were as follows: 28 (17%) claimed at least one first-degree relative with PC; 54 (32%) claimed a first, second, or third-degree relative with PC; 24 (14%) had no known family history of PC; and 95 (57%) claimed a first-degree relative with another cancer (breast [37], prostate [25], colon [18], ovarian [9], uterine [6], and gastric [2]). Germline testing was pursued by 138 (83%) pts: 25 (18%) were found to have a pathogenic variant and 50 (36%) a variant of uncertain significance. Pathogenic variants were most commonly identified in ATM (24%), BRCA2 (20%), PALB2 (12%), and CDKN2A (8%). Variants were also observed in DIS3L2, HOXB13, MITF, MUTYH (heterozygote), NTHL1 (compound heterozygote), RAD50, PRSS1, and SDHA. Among pts that had a pathogenic variant, cascade testing was performed in 11 families (44%) for 29 individuals. Conclusions: Our data suggest that the referral of PC pts to genetics has increased following updated ASCO/NCCN guidelines. However, improved adherence to genetic counseling is needed. ATM and BRCA2 were the most common germline mutations observed. More effort to increase awareness of genetic testing and its potential implications for pts and their families is warranted and might reduce cancellations and missed visits.