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Background: Pancreatic ductal adenocarcinoma (PDAC) surveillance is recommended for some individuals with a pathogenic or likely pathogenic variant (PV/LPV) in a PDAC susceptibility gene; the recommendation is often dependent on family history of PDAC. This study aimed to describe PDAC family history in individuals with PDAC who underwent genetic testing to determine the appropriateness of including a family history requirement in these recommendations. Methods: Individuals with PDAC with a germline heterozygous PV/LPV in ATM, BRCA1, BRCA2, EPCAM, MLH1, MSH2, MSH6, PALB2, or PMS2 (PV/LPV carriers) were assessed for family history of PDAC in first‐degree relatives (FDRs) or second‐degree relatives (SDRs) from nine institutions. A control group of individuals with PDAC without a germline PV/LPV was also assessed. Results: The study included 196 PV/LPV carriers and 1184 controls. In the PV/LPV carriers, 25.5% had an affected FDR and/or SDR compared to 16.9% in the control group (p =.004). PV/LPV carriers were more likely to have an affected FDR compared to the controls (p =.003) but there was no statistical difference when assessing only affected SDRs (p =.344). Conclusions: Most PV/LPV carriers who developed PDAC did not have a close family history of PDAC and would not have met most current professional societies' recommendations for consideration of PDAC surveillance before diagnosis. However, PV/LPV carriers were significantly more likely to have a family history of PDAC, particularly an affected FDR. These findings support family history as a risk modifier in PV/LPV carriers, and highlight the need to identify other risk factors. Results from this multicenter study show that individuals with pancreatic cancer and a germline pathogenic variant in ATM, BRCA1, BRCA2, EPCAM, MLH1, MSH2, MSH6, PALB2, or PMS2 are more likely to have a family history of pancreatic cancer, especially a first‐degree relative, compared to individuals with pancreatic cancer and no germline pathogenic variant. However, most individuals diagnosed with pancreatic cancer who have a germline pathogenic variant in one of these genes would not have met current guidelines for pancreatic surveillance because of a lack of family history. [ABSTRACT FROM AUTHOR]

Aims: The hallmark of Lynch syndrome (LS) is DNA mismatch repair protein (MMR) deficiency. Recently, MMR deficiency in non‐neoplastic colonic crypts has been identified as a novel indicator of LS. We aimed to determine whether MMR‐deficient non‐neoplastic endometrial glands can distinguish patients with and without LS, and to compare the level of MMR deficiency in the normal endometrium and colon in LS patients. Methods and results: We evaluated the immunohistochemical expression of MMR proteins in the normal endometrial mucosa from 64 patients, including 34 patients with confirmed LS (17 with endometrial cancer and 17 without cancer), 30 patients with endometrial cancer without LS (10 with tumours with MLH1 promoter hypermethylation and 20 with MMR‐proficient tumours), and in the normal colonic mucosa from 30 LS patients. MMR‐deficient non‐neoplastic endometrial glands were identified in 47% of LS patients and in no patients without LS (P < 0.001). MMR‐deficient non‐neoplastic glands were more often identified in LS patients with endometrial cancer (65%) than in those without endometrial cancer (29%) (P = 0.04). In contrast to what was seen in the normal colon, MMR‐deficient glands in the normal endometrium were seen as large, contiguous groups, ranging in number from two to 101 (87% versus 45%, P = 0.02). MMR‐deficient glands were identified at a higher density in the endometrium than in the colon in LS patients (median number of MMR‐deficient glands, 22 versus two, P = 0.02). Conclusions: Our findings indicate that MMR‐deficient non‐neoplastic endometrial glands constitute an indicator of LS, and that MMR‐deficient glands in the endometrium are present in a pattern of contiguous large groups. [ABSTRACT FROM AUTHOR]

The identification of patient outcomes unique to the field of genetic counseling has become a recent priority of the profession. Current health‐care efforts have targeted patient engagement as an outcome capable of improving population health and reducing health‐care costs. This study analyzed patient engagement levels among 182 participants who underwent genetic counseling for gastrointestinal (GI) cancer risk assessment in an outpatient specialty clinic. Patients seen at the UPMC Hereditary GI Tumor Program completed a validated patient engagement measure, the Altarum Consumer Engagement (ACE), prior to undergoing genetic counseling and again three months after enrollment. Paired t test analysis was conducted to assess the changes in Total ACE scores, and within the following three domains: Navigation, Informed Choice, and Commitment. In the sample of 182 participants, Total ACE scores increased after genetic counseling (by 5.7%; p < .0001), as did all three domains (Commitment p = .0008; Navigation p = .0008; and Informed Choice p = .0016). This study is the first known report of patient engagement levels in individuals undergoing genetic counseling in a specialty cancer clinic and suggests that genetic counseling improves patient engagement levels. [ABSTRACT FROM AUTHOR]

Background: Germline genetic testing currently is recommended for patients with pancreatic ductal adenocarcinoma (PDAC). In the current study, the authors assessed how often results are communicated to first-degree relatives within 3 months and the emotional impact of testing on patients.Methods: A total of 148 patients who were newly diagnosed with PDAC and who had undergone testing of 32 cancer susceptibility genes at 3 academic centers were selected; 71% participated. Subjects completed the Multidimensional Impact of Cancer Risk Assessment (MICRA) and a family communication survey. The results of both surveys were assessed at 3 months according to the genetic test result (positive, negative, or variant of unknown significance [VUS]) and whether a patient met criteria for genetic testing.Results: A total of 99 patients completed the MICRA survey and 104 completed the family communication survey. The average age of the patients was 67 years, 47% were female, 29% had stage III/IV (AJCC 8th edition) disease, and 42% met genetic testing criteria. Approximately 80% of patients told at least 1 first-degree relative about their result. There was a trend toward greater disclosure among patients who tested positive (93% vs 77% for those with a VUS result [P = .149] and 74% for those who tested negative [P = .069]). Patients not meeting genetic testing criteria were less likely to disclose results (69% vs 93%; P = .003). MICRA scores did not differ by test result, age, stage of disease, or sex.Conclusions: The rate of result communication was high, although it was lower among patients who did not meet genetic testing criteria, those who tested negative, or those who had a VUS result. Testing-associated distress was similar across patient groups, and was comparable to that reported by other patients with cancer. Improved communication for all patients is crucial given the prognosis of PDAC, which limits time for disclosure. [ABSTRACT FROM AUTHOR]

BACKGROUND: The objective of this study was to investigate the prevalence of pathogenic germline variants (PGVs) in 32 cancer susceptibility genes in individuals with newly diagnosed pancreatic ductal adenocarcinoma (PDAC). A key secondary objective was to evaluate how often PGVs would have been undetected with existing genetic testing criteria. METHODS: From May 2016 through May 2017, this multicenter cohort study enrolled consecutive patients aged 18 to 89 years with histologically confirmed PDAC diagnosed within the previous 12 weeks. Demographics, medical histories, and 3‐generation pedigrees were collected from participants who provided samples for germline DNA analysis. RESULTS: Four hundred nineteen patients were deemed eligible, 302 were enrolled, and 298 were included in the final cohort. Clinically actionable variants were reported in 29 PDAC patients (9.7%), with 23 (7.7%) having a PGV associated with an increased risk for PDAC. Six of 23 individuals (26%) with PDAC‐associated gene mutations did not meet currently established genetic testing criteria. According to guideline‐based genetic testing, only 11 of the 23 PGVs (48%) in known PDAC genes would have been detected. Six additional patients (2%) had PGVs associated with an increased risk for other cancers. CONCLUSIONS: These findings support the significant prevalence of PGVs associated with PDAC and the limitations of current paradigms for selecting patients for genetic testing, and they thereby lend support for universal germline multigene genetic testing in this population. This study suggests that a substantial proportion of pancreatic cancer cases may be explained by mutations in cancer susceptibility genes and points to limitations of genetic testing criteria in identifying genetic risk for this disease. These findings lend support for universal germline genetic testing in patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: Approximately 10% of pancreatic adenocarcinoma (PC) cases are attributed to hereditary causes. Individuals with PC and a personal history of another cancer associated with hereditary breast and ovarian cancer (HBOC) or Lynch syndrome (LS) may be more likely to carry germline mutations.Methods: Participants with PC and a history of cancer were selected from a pancreatic disease registry. Of 1296 individuals with PC, 149 had a relevant history of cancer. If banked DNA was available, a multigene panel was performed for individuals who had not 1) previously had a mutation identified through clinical testing or 2) undergone clinical multigene panel testing with no mutations detected.Results: Twenty-two of 124 individuals with PC and another HBOC- or LS-related cancer who underwent genetic testing had a mutation identified in a PC susceptibility gene (18%). If prostate cancer is excluded, the mutation prevalence increased to 23% (21/93). Mutation carriers were more likely to have more than 1 previous cancer diagnosis (P = .001), to have had clinical genetic testing (P = .001), and to meet National Comprehensive Cancer Network (NCCN) genetic testing criteria (P < .001). Approximately 23% of mutation carriers did not meet NCCN HBOC or LS testing guidelines based on their personal cancer history and reported cancer history in first-degree relatives.Conclusion: At least 18% of individuals with PC and a personal history of other HBOC- or LS-related cancers carry mutations in a PC susceptibility gene based on our data, suggesting that criteria for genetic testing in individuals with PC should include consideration of previous cancer history. Cancer 2018;124:1691-700. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]