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Gastroenterology and Hepatology

An Emerging Paradigm for Germline Testing in Pancreatic Ductal Adenocarcinoma and Immediate Implications for Clinical PracticeA Review

Educational Objective
To learn the role of germline genetic testing in patients with pancreatic ductal adenocarcinoma
1 Credit CME
JAMA Oncology
May 1, 2020
Review
Michael Rainone, MBBCh1,2;
Isha Singh, MBBS1,2;
Erin E. Salo-Mullen, MS1;
Zsofia K. Stadler, MD1,3;
Eileen M. O’Reilly, MD1,3,4
Author Affiliations
  • 1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
  • 2Department of Medicine, Mount Sinai St Luke’s and Mount Sinai West Hospitals, Icahn School of Medicine at Mount Sinai, New York, New York
  • 3David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York
  • 4Department of Medicine, Weill Cornell Medicine, New York, New York
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Abstract

Importance  Pancreatic ductal adenocarcinoma (PDAC) is a malignant neoplasm with a rising incidence and is a leading public health challenge. Pancreatic ductal adenocarcinoma has been well characterized genomically, with findings of therapeutic actionability that have substantive implications for clinical practice based on recent high-level evidence.

Observations  Pathogenic germline alterations (PGAs) are relatively common in individuals with PDAC, as evidenced in multiple recent data sets, with a frequency of approximately 10%. The most common PGAs are in BRCA1, BRCA2, and ATM and more rarely in PALB2, MLH1, MSH2, MSH6, PMS2, CDKN2A, and TP53, among others, with an aggregate frequency of 3.8% to 9.7%. These PGAs are of key interest owing to therapeutic actionability and the downstream identification of at-risk family members and possible hereditary cancer syndromes. Approximately 3% to 7% of individuals with PDAC harbor a BRCA1 or BRCA2 mutation, which are among the most frequently mutated genes in PDAC. Recent updates to the American Society of Clinical Oncology and the National Comprehensive Cancer Network guidelines recommend risk assessment for all individuals with PDAC irrespective of personal or family history or ethnicity. Treatment implications include the use of checkpoint inhibitor therapy for mismatch repair–deficient PDAC and the validation of poly-ADP (adenosine diphosphate)-ribose polymerase inhibitor (PARPi) therapy as a maintenance strategy in platinum-sensitive PDAC.

Conclusions and Relevance  With increasing evidence and slow improvement of outcomes, PDAC has entered the era of precision medicine. Germline mutations have been identified in key genes with an aggregate frequency of 3.8% to 9.7%, several of which are therapeutically actionable with platinum, PARPi, and checkpoint inhibitor therapy. Potential therapeutic targets need to be actively sought and identified.

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Gastroenterology Gastrointestinal Cancer Oncology Pancreatic Cancer Pancreatic Disease Cancer Genetics Gastroenterology and Hepatology
Article Information

Accepted for Publication: October 7, 2019.

Corresponding Author: Eileen M. O’Reilly, MD, Department of Medicine, Memorial Sloan Kettering Cancer Center, 300 E 66th St, Office 1021, New York, NY 10065 (oreillye@mskcc.org).

Published Online: February 13, 2020. doi:10.1001/jamaoncol.2019.5963

Author Contributions: Drs Rainone, Singh, and O’Reilly contributed equally to this work. Drs Stadler and O’Reilly had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Rainone, Singh, O’Reilly.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Rainone, Singh, Stadler, O’Reilly.

Critical revision of the manuscript for important intellectual content: All authors.

Obtained funding: O’Reilly.

Administrative, technical, or material support: Rainone, Salo-Mullen, O’Reilly.

Supervision: O’Reilly.

Conflict of Interest Disclosures: Dr Stadler reported that immediate family members hold consulting/advisory roles within the field of ophthalmology with Allergan, Adverum Biotechnologies, Alimera Sciences, Inc, BioMarin Pharmaceuticals, Inc, Fortress Biotech, Inc, Genentech, Inc, Novartis International AG, Optos, Regeneron Pharmaceuticals, Inc, Regenxbio, Inc, and Spark Therapeutics. Dr O’Reilly reported receiving personal fees from Merck & Co and AstraZeneca and grants from AstraZeneca during the conduct of the study and grants from Genentech, Inc, Roche, Bristol-Myers Squibb, Celgene Corporation, MabVax Therapeutics Holdings, Inc, Acta Biologica, and Silenseed, Ltd, as well as personal fees from Polaris Pharmaceuticals, Sobi, Bayer, Targovax, and CytomX outside the submitted work. No other disclosures were reported.

Funding/Support: This study was supported by Cancer Center Support grant P30 CA-008748-48, David M. Rubenstein Center for Pancreatic Cancer Research (principal investigator, Craig Thompson, MD).

Role of the Funder/Sponsor: The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Rahib  L , Smith  BD , Aizenberg  R , Rosenzweig  AB , Fleshman  JM , Matrisian  LM .  Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States.   Cancer Res. 2014;74(11):2913-2921. doi:10.1158/0008-5472.CAN-14-0155 PubMedGoogle ScholarCrossref
2.
Siegel  RL , Miller  KD , Jemal  A .  Cancer statistics, 2016.   CA Cancer J Clin. 2016;66(1):7-30. doi:10.3322/caac.21332PubMedGoogle ScholarCrossref
3.
Golan  T , Hammel  P , Reni  M ,  et al.  Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer.   N Engl J Med. 2019;381(4):317-327. doi:10.1056/NEJMoa1903387PubMedGoogle ScholarCrossref
4.
Hu  ZI , Shia  J , Stadler  ZK ,  et al.  Evaluating mismatch repair deficiency in pancreatic adenocarcinoma: challenges and recommendations.   Clin Cancer Res. 2018;24(6):1326-1336. doi:10.1158/1078-0432.CCR-17-3099PubMedGoogle ScholarCrossref
5.
Le  DT , Durham  JN , Smith  KN ,  et al.  Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.   Science. 2017;357(6349):409-413. doi:10.1126/science.aan6733PubMedGoogle ScholarCrossref
6.
Shindo  K , Yu  J , Suenaga  M ,  et al.  Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma.   J Clin Oncol. 2017;35(30):3382-3390. doi:10.1200/JCO.2017.72.3502PubMedGoogle ScholarCrossref
7.
Hu  C , Hart  SN , Bamlet  WR ,  et al.  Prevalence of pathogenic mutations in cancer predisposition genes among pancreatic cancer patients.   Cancer Epidemiol Biomarkers Prev. 2016;25(1):207-211. doi:10.1158/1055-9965.EPI-15-0455PubMedGoogle ScholarCrossref
8.
Lowery  MA , Wong  W , Jordan  EJ ,  et al.  Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms.   J Natl Cancer Inst. 2018;110(10):1067-1074. doi:10.1093/jnci/djy024PubMedGoogle ScholarCrossref
9.
Yurgelun  MB , Chittenden  AB , Morales-Oyarvide  V ,  et al.  Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer.   Genet Med. 2019;21(1):213-223. doi:10.1038/s41436-018-0009-5PubMedGoogle ScholarCrossref
10.
Hu  C , Hart  SN , Polley  EC ,  et al.  Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer.   JAMA. 2018;319(23):2401-2409. doi:10.1001/jama.2018.6228PubMedGoogle ScholarCrossref
11.
Raimondi  S , Maisonneuve  P , Lowenfels  AB .  Epidemiology of pancreatic cancer: an overview.   Nat Rev Gastroenterol Hepatol. 2009;6(12):699-708. doi:10.1038/nrgastro.2009.177PubMedGoogle ScholarCrossref
12.
Hu  C , LaDuca  H , Shimelis  H ,  et al.  Multigene hereditary cancer panels reveal high-risk pancreatic cancer susceptibility genes [published online July 25, 2018].   JCO Precis Oncol. doi:10.1200/PO.17.00291Google Scholar
13.
Kurian  AW , Hughes  E , Handorf  EA ,  et al.  Breast and ovarian cancer penetrance estimates derived from germline multiple-gene sequencing results in women [published online June 27, 2017].   JCO Precis Oncol. doi:10.1200/PO.16.00066Google Scholar
14.
Kurian  AW , Ward  KC , Howlader  N ,  et al.  Genetic testing and results in a population-based cohort of breast cancer patients and ovarian cancer patients.   J Clin Oncol. 2019;37(15):1305-1315. doi:10.1200/JCO.18.01854PubMedGoogle ScholarCrossref
15.
Grant  RC , Selander  I , Connor  AA ,  et al.  Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer.   Gastroenterology. 2015;148(3):556-564. doi:10.1053/j.gastro.2014.11.042PubMedGoogle ScholarCrossref
16.
Holter  S , Borgida  A , Dodd  A ,  et al.  Germline BRCA mutations in a large clinic-based cohort of patients with pancreatic adenocarcinoma.   J Clin Oncol. 2015;33(28):3124-3129. doi:10.1200/JCO.2014.59.7401PubMedGoogle ScholarCrossref
17.
Mandelker  D , Zhang  L , Kemel  Y ,  et al.  Mutation detection in patients with advanced cancer by universal sequencing of cancer-related genes in tumor and normal DNA vs guideline-based germline testing.   JAMA. 2017;318(9):825-835. doi:10.1001/jama.2017.11137PubMedGoogle ScholarCrossref
18.
Brand  R , Borazanci  E , Speare  V ,  et al.  Prospective study of germline genetic testing in incident cases of pancreatic adenocarcinoma.   Cancer. 2018;124(17):3520-3527. doi:10.1002/cncr.31628 PubMedGoogle ScholarCrossref
19.
Taherian  N , Saam  J , Larson  K ,  et al. Hereditary cancer genetic testing among patients with pancreatic cancer. Paper presented at: American Society for Clinical Oncology Annual Meeting; June 3, 2019; Chicago, IL.
20.
Kaufman  B , Shapira-Frommer  R , Schmutzler  RK ,  et al.  Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation.   J Clin Oncol. 2015;33(3):244-250. doi:10.1200/JCO.2014.56.2728 PubMedGoogle ScholarCrossref
21.
Le  DT , Uram  JN , Wang  H ,  et al.  PD-1 blockade in tumors with mismatch-repair deficiency.   N Engl J Med. 2015;372(26):2509-2520. doi:10.1056/NEJMoa1500596 PubMedGoogle ScholarCrossref
22.
National Comprehensive Cancer Network. Pancreatic adenocarcinoma, version 2.2019. https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Published 2019. Accessed April 30, 2019.
23.
Stoffel  EM , McKernin  SE , Brand  R ,  et al.  Evaluating susceptibility to pancreatic cancer: ASCO provisional clinical opinion.   J Clin Oncol. 2019;37(2):153-164. doi:10.1200/JCO.18.01489 PubMedGoogle ScholarCrossref
24.
Findlay  GM , Daza  RM , Martin  B ,  et al.  Accurate classification of BRCA1 variants with saturation genome editing.   Nature. 2018;562(7726):217-222. doi:10.1038/s41586-018-0461-z PubMedGoogle ScholarCrossref
25.
Jonsson  P , Bandlamudi  C , Cheng  ML ,  et al.  Tumour lineage shapes BRCA-mediated phenotypes.   Nature. 2019;571(7766):576-579. doi:10.1038/s41586-019-1382-1 PubMedGoogle ScholarCrossref
26.
Singh  RR , Goldberg  J , Varghese  AM , Yu  KH , Park  W , O’Reilly  EM .  Genomic profiling in pancreatic ductal adenocarcinoma and a pathway towards therapy individualization: a scoping review.   Cancer Treat Rev. 2019;75:27-38. doi:10.1016/j.ctrv.2019.03.003 PubMedGoogle ScholarCrossref
27.
Lowery  MAJ , Jordan  EJ , Basturk  O ,  et al.  Real-time genomic profiling of pancreatic ductal adenocarcinoma: potential actionability and correlation with clinical phenotype.   Clin Cancer Res. 2017;23(20):6094-6100. doi:10.1158/1078-0432.CCR-17-0899 PubMedGoogle ScholarCrossref
28.
Pishvaian  MJ , Bender  RJ , Halverson  D ,  et al.  Molecular profiling of patients with pancreatic cancer: initial results from the Know Your Tumor initiative.   Clin Cancer Res. 2018;24(20):5018-5027. doi:10.1158/1078-0432.CCR-18-0531 PubMedGoogle Scholar
29.
Mandelker  D , Donoghue  M , Talukdar  S ,  et al.  Germline-focussed analysis of tumour-only sequencing: recommendations from the ESMO Precision Medicine Working Group.   Ann Oncol. 2019;30(8):1221-1231. doi:10.1093/annonc/mdz136 PubMedGoogle ScholarCrossref
30.
Salo-Mullen  EE , O’Reilly  EM , Kelsen  DP ,  et al.  Identification of germline genetic mutations in patients with pancreatic cancer.   Cancer. 2015;121(24):4382-4388. doi:10.1002/cncr.29664PubMedGoogle ScholarCrossref
31.
Daly  MB , Pilarski  R , Berry  M ,  et al. Genetic/familial high-risk assessment: breast and ovarian, version 3.2019. https://www.partnershipagainstcancer.ca/db-sage/sage20181503/. Published 2019. Accessed July 25, 2019.
32.
Antoniou  AC , Casadei  S , Heikkinen  T ,  et al.  Breast-cancer risk in families with mutations in PALB2.   N Engl J Med. 2014;371(6):497-506. doi:10.1056/NEJMoa1400382PubMedGoogle ScholarCrossref
33.
Choi  M , Kipps  T , Kurzrock  R .  ATM mutations in cancer: therapeutic implications.   Mol Cancer Ther. 2016;15(8):1781-1791. doi:10.1158/1535-7163.MCT-15-0945PubMedGoogle ScholarCrossref
34.
Dowty  JG , Win  AK , Buchanan  DD ,  et al.  Cancer risks for MLH1 and MSH2 mutation carriers.   Hum Mutat. 2013;34(3):490-497. doi:10.1002/humu.22262PubMedGoogle ScholarCrossref
35.
Bellcross  CA , Bedrosian  SR , Daniels  E ,  et al.  Implementing screening for Lynch syndrome among patients with newly diagnosed colorectal cancer: summary of a public health/clinical collaborative meeting.   Genet Med. 2012;14(1):152-162. doi:10.1038/gim.0b013e31823375ea PubMedGoogle ScholarCrossref
36.
McWilliams  RR , Wieben  ED , Rabe  KG ,  et al.  Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling.   Eur J Hum Genet. 2011;19(4):472-478. doi:10.1038/ejhg.2010.198 PubMedGoogle ScholarCrossref
37.
Resta  N , Pierannunzio  D , Lenato  GM ,  et al; AIFEG.  Cancer risk associated with STK11/LKB1 germline mutations in Peutz-Jeghers syndrome patients: results of an Italian multicenter study.   Dig Liver Dis. 2013;45(7):606-611. doi:10.1016/j.dld.2012.12.018 PubMedGoogle ScholarCrossref
38.
Schneider  K , Zelley  K , Nichols  KE , Garber  J . Li-Fraumeni syndrome. In: Adam  MP , Ardinger  HH , Pagon  RA ,  et al, eds.  GeneReviews. Seattle: University of Washington; June 3, 2013.
39.
Whitcomb  DC , Applebaum  S , Martin  SP .  Hereditary pancreatitis and pancreatic carcinoma.   Ann N Y Acad Sci. 1999;880:201-209. doi:10.1111/j.1749-6632.1999.tb09524.x PubMedGoogle ScholarCrossref
40.
Golan  T , Sella  T , O’Reilly  EM ,  et al.  Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer.   Br J Cancer. 2017;116(6):697-702. doi:10.1038/bjc.2017.19PubMedGoogle ScholarCrossref
41.
Sehdev  A , Gbolahan  O , Hancock  BA ,  et al.  Germline and somatic DNA damage repair gene mutations and overall survival in metastatic pancreatic adenocarcinoma patients treated with FOLFIRINOX.   Clin Cancer Res. 2018;24(24):6204-6211. doi:10.1158/1078-0432.CCR-18-1472PubMedGoogle ScholarCrossref
42.
Kondo  T , Kanai  M , Kou  T ,  et al.  Association between homologous recombination repair gene mutations and response to oxaliplatin in pancreatic cancer.   Oncotarget. 2018;9(28):19817-19825. doi:10.18632/oncotarget.24865PubMedGoogle ScholarCrossref
43.
Golan  T , Kanji  ZS , Epelbaum  R ,  et al.  Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers.   Br J Cancer. 2014;111(6):1132-1138. doi:10.1038/bjc.2014.418 PubMedGoogle ScholarCrossref
44.
Lowery  MA , Kelsen  DP , Stadler  ZK ,  et al.  An emerging entity: pancreatic adenocarcinoma associated with a known BRCA mutation: clinical descriptors, treatment implications, and future directions.   Oncologist. 2011;16(10):1397-1402. doi:10.1634/theoncologist.2011-0185 PubMedGoogle ScholarCrossref
45.
Pishvaian  MJ , Blais  EM , Brody  JR ,  et al.  Outcomes in pancreatic adenocarcinoma (PDA) patients (pts) with genetic alterations in DNA damage repair (DDR) pathways: results from the Know Your Tumor (KYT) program.   J Clin Oncol. 2019;37(4)(suppl):191-191. doi:10.1200/JCO.2019.37.4_suppl.191 Google ScholarCrossref
46.
National Comprehensive Cancer Network. Pancreatic adenocarcinoma, version 1.2019. https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Published 2018. Accessed January 15, 2019.
47.
de Bono  J , Ramanathan  RK , Mina  L ,  et al.  Phase I, dose-escalation, two-part trial of the PARP inhibitor talazoparib in patients with advanced germline BRCA1/2 mutations and selected sporadic cancers.   Cancer Discov. 2017;7(6):620-629. doi:10.1158/2159-8290.CD-16-1250 PubMedGoogle ScholarCrossref
48.
Shroff  RT , Hendifar  A , McWilliams  RR ,  et al.  Rucaparib monotherapy in patients with pancreatic cancer and a known deleterious BRCA mutation.  [published online May 16, 2018]. JCO Precis Oncol. doi:10.1200/PO.17.00316Google Scholar
49.
Lowery  MA , Kelsen  DP , Capanu  M ,  et al.  Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma.   Eur J Cancer. 2018;89:19-26. doi:10.1016/j.ejca.2017.11.004 PubMedGoogle ScholarCrossref
50.
O’Reilly  EM , Lee  JW , Lowery  MA ,  et al.  Phase 1 trial evaluating cisplatin, gemcitabine, and veliparib in 2 patient cohorts: germline BRCA mutation carriers and wild-type BRCA pancreatic ductal adenocarcinoma.   Cancer. 2018;124(7):1374-1382. doi:10.1002/cncr.31218 PubMedGoogle ScholarCrossref
51.
Reiss Binder  KA , Mick  R , O’Hara  M ,  et al.  A phase II, single arm study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic mutation in BRCA1, BRCA2 or PALB2 [published online July 2019].   Cancer Res. doi:10.1158/1538-7445.AM2019-CT234Google Scholar
52.
Latham  A , Srinivasan  P , Kemel  Y ,  et al.  Microsatellite instability is associated with the presence of Lynch syndrome pan-cancer.   J Clin Oncol. 2019;37(4):286-295. doi:10.1200/JCO.18.00283 PubMedGoogle ScholarCrossref
53.
Yuza  K , Nagahashi  M , Watanabe  S , Takabe  K , Wakai  T .  Hypermutation and microsatellite instability in gastrointestinal cancers.   Oncotarget. 2017;8(67):112103-112115. doi:10.18632/oncotarget.22783 PubMedGoogle ScholarCrossref
54.
Klümpen  HJ , Queiroz  KC , Spek  CA ,  et al.  mTOR inhibitor treatment of pancreatic cancer in a patient with Peutz-Jeghers syndrome.   J Clin Oncol. 2011;29(6):e150-e153. doi:10.1200/JCO.2010.32.7825 PubMedGoogle ScholarCrossref
55.
Min  A , Im  SA , Yoon  YK ,  et al.  RAD51C-deficient cancer cells are highly sensitive to the PARP inhibitor olaparib.   Mol Cancer Ther. 2013;12(6):865-877. doi:10.1158/1535-7163.MCT-12-0950 PubMedGoogle ScholarCrossref
56.
Aguirre  AJ , Nowak  JA , Camarda  ND ,  et al.  Real-time genomic characterization of advanced pancreatic cancer to enable precision medicine.   Cancer Discov. 2018;8(9):1096-1111. doi:10.1158/2159-8290.CD-18-0275 PubMedGoogle ScholarCrossref
57.
Robson  M , Offit  K .  Clinical practice: management of an inherited predisposition to breast cancer.   N Engl J Med. 2007;357(2):154-162. doi:10.1056/NEJMcp071286 PubMedGoogle ScholarCrossref
58.
Syngal  S , Brand  RE , Church  JM , Giardiello  FM , Hampel  HL , Burt  RW ; American College of Gastroenterology.  ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes.   Am J Gastroenterol. 2015;110(2):223-262. doi:10.1038/ajg.2014.435 PubMedGoogle ScholarCrossref
59.
US Preventive Services Task Force. Draft recommendation statement: pancreatic cancer: screening. https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/pancreatic-cancer-screening1. Published 2019. Accessed June 16, 2019.
60.
US Preventive Services Task Force. Screening for pancreatic cancer: a systematic evidence review for the US Preventive Services Task Force. https://www.uspreventiveservicestaskforce.org/Page/Document/draft-evidence-review/pancreatic-cancer-screening1. Published February 2019. Accessed July 25, 2019.
61.
Chaffee  KG , Oberg  AL , McWilliams  RR ,  et al.  Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history.   Genet Med. 2018;20(1):119-127. doi:10.1038/gim.2017.85 PubMedGoogle ScholarCrossref
62.
Canto  MI , Almario  JA , Schulick  RD ,  et al.  Risk of neoplastic progression in individuals at high risk for pancreatic cancer undergoing long-term surveillance.   Gastroenterology. 2018;155(3):740-751.e2. doi:10.1053/j.gastro.2018.05.035PubMedGoogle ScholarCrossref
63.
Vasen  H , Ibrahim  I , Ponce  CG ,  et al.  Benefit of surveillance for pancreatic cancer in high-risk individuals: outcome of long-term prospective follow-up studies from three European expert centers.   J Clin Oncol. 2016;34(17):2010-2019. doi:10.1200/JCO.2015.64.0730 PubMedGoogle ScholarCrossref
64.
Lynce  F , Isaacs  C .  How far do we go with genetic evaluation? gene, panel, and tumor testing.   Am Soc Clin Oncol Educ Book. 2016;35:e72-e78. doi:10.14694/EDBK_160391 PubMedGoogle ScholarCrossref
65.
Stoll  K , Kubendran  S , Cohen  SA .  The past, present and future of service delivery in genetic counseling: keeping up in the era of precision medicine.   Am J Med Genet C Semin Med Genet. 2018;178(1):24-37. doi:10.1002/ajmg.c.31602 PubMedGoogle ScholarCrossref
66.
Okur  V , Chung  WK .  The impact of hereditary cancer gene panels on clinical care and lessons learned.   Cold Spring Harb Mol Case Stud. 2017;3(6):a002154. doi:10.1101/mcs.a002154 PubMedGoogle Scholar
67.
Casneuf  VF , Fonteyne  P , Van Damme  N ,  et al.  Expression of SGLT1, Bcl-2 and p53 in primary pancreatic cancer related to survival.   Cancer Invest. 2008;26(8):852-859. doi:10.1080/07357900801956363 PubMedGoogle ScholarCrossref
68.
Halfdanarson  TR , Wang  L , Bamlet  WR ,  et al.  Mitochondrial genetic polymorphisms do not predict survival in patients with pancreatic cancer.   Cancer Epidemiol Biomarkers Prev. 2008;17(9):2512-2513. doi:10.1158/1055-9965.EPI-08-0460 PubMedGoogle ScholarCrossref
69.
Invitae Pancreatic Cancer Panel. Test description. https://www.invitae.com/en/physician/tests/01261/. Accessed June 26, 2019.
70.
Suzuki  T , Matsuo  K , Sawaki  A ,  et al.  Alcohol drinking and one-carbon metabolism-related gene polymorphisms on pancreatic cancer risk.   Cancer Epidemiol Biomarkers Prev. 2008;17(10):2742-2747. doi:10.1158/1055-9965.EPI-08-0470 PubMedGoogle ScholarCrossref
71.
Bao  Y , Michaud  DS .  Physical activity and pancreatic cancer risk: a systematic review.   Cancer Epidemiol Biomarkers Prev. 2008;17(10):2671-2682. doi:10.1158/1055-9965.EPI-08-0488 PubMedGoogle ScholarCrossref
72.
Permuth-Wey  J , Egan  KM .  Family history is a significant risk factor for pancreatic cancer: results from a systematic review and meta-analysis.   Fam Cancer. 2009;8(2):109-117. doi:10.1007/s10689-008-9214-8 PubMedGoogle ScholarCrossref
73.
Xiong  HQ , Varadhachary  GR , Blais  JC , Hess  KR , Abbruzzese  JL , Wolff  RA .  Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer.   Cancer. 2008;113(8):2046-2052. doi:10.1002/cncr.23810 PubMedGoogle ScholarCrossref
74.
Balmaña  J , Digiovanni  L , Gaddam  P ,  et al.  Conflicting interpretation of genetic variants and cancer risk by commercial laboratories as assessed by the prospective registry of multiplex testing.   J Clin Oncol. 2016;34(34):4071-4078. doi:10.1200/JCO.2016.68.4316 PubMedGoogle ScholarCrossref
75.
Hoffman-Andrews  L .  The known unknown: the challenges of genetic variants of uncertain significance in clinical practice.   J Law Biosci. 2018;4(3):648-657. doi:10.1093/jlb/lsx038 PubMedGoogle ScholarCrossref
76.
ClinicalTrials.gov. A Registry for BRCA Mutation Carriers With Pancreatic Ductal Adenocarcinoma. NCT01983410. https://clinicaltrials.gov/ct2/show/NCT01983410. Accessed July 25, 2019.
77.
ClinicalTrials.gov. GENetic Education Risk Assessment and TEsting Study (GENERATE). NCT03762590. https://clinicaltrials.gov/ct2/show/NCT03762590. Accessed July 25, 2019.
78.
Tandy-Connor  S , Guiltinan  J , Krempely  K ,  et al.  False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care.   Genet Med. 2018;20(12):1515-1521. doi:10.1038/gim.2018.38PubMedGoogle ScholarCrossref
79.
ACMG Board of Directors.  Direct-to-consumer genetic testing: a revised position statement of the American College of Medical Genetics and Genomics.   Genet Med. 2016;18(2):207-208. doi:10.1038/gim.2015.190PubMedGoogle ScholarCrossref
80.
Niu  B , Ye  K , Zhang  Q ,  et al.  MSIsensor: microsatellite instability detection using paired tumor-normal sequence data.   Bioinformatics. 2014;30(7):1015-1016. doi:10.1093/bioinformatics/btt755PubMedGoogle ScholarCrossref
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