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Managing Germline Findings from Molecular Testing in Precision Oncology

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Precision Cancer Medicine

Abstract

Molecular genetic testing of the germline for hereditary cancer risk and molecular testing of tumor tissue for therapeutic decision making are no longer clearly distinct. Here we review how changes in sequencing technology have impacted use of germline and tumor molecular testing, implications for identifying incidental pathogenic germline variants through tumor testing, relevance of pathogenic germline variants in cancer care and prevention, and emerging research guiding clinical practice in this area.

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References

  1. Van Allen EM, Wagle N, Levy MA (2013) Clinical analysis and interpretation of cancer genome data. J Clin Oncol 31(15):1825–1833. https://doi.org/10.1200/JCO.2013.48.7215

    Article  PubMed  PubMed Central  Google Scholar 

  2. www.fda.gov [cited 2017 May]

  3. Jones S, Anagnostou V, Lytle K, Parpart-Li S, Nesselbush M, Riley DR et al (2015) Personalized genomic analyses for cancer mutation discovery and interpretation. Sci Transl Med 7(283):283ra53. https://doi.org/10.1126/scitranslmed.aaa7161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD et al (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372(26):2509–2520. https://doi.org/10.1056/NEJMoa1500596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmana J et al (2015) Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol 33(3):244–250. https://doi.org/10.1200/JCO.2014.56.2728

    Article  CAS  PubMed  Google Scholar 

  6. Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ et al (2017) Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 317(23):2402–2416. https://doi.org/10.1001/jama.2017.7112

    Article  CAS  PubMed  Google Scholar 

  7. Passaperuma K, Warner E, Causer PA, Hill KA, Messner S, Wong JW et al (2012) Long-term results of screening with magnetic resonance imaging in women with BRCA mutations. Br J Cancer 107(1):24–30. https://doi.org/10.1038/bjc.2012.204. PubMed PMID: 22588560; PubMed Central PMCID: PMCPMC3389408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Narod SA, Brunet JS, Ghadirian P, Robson M, Heimdal K, Neuhausen SL et al (2000) Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study hereditary breast cancer clinical study group. Lancet 356(9245):1876–1881

    Article  CAS  PubMed  Google Scholar 

  9. Narod SA, Risch H, Moslehi R, Dorum A, Neuhausen S, Olsson H et al (1998) Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary ovarian cancer clinical study group. N Engl J Med 339(7):424–428. https://doi.org/10.1056/NEJM199808133390702

    Article  CAS  PubMed  Google Scholar 

  10. Hartmann LC, Sellers TA, Schaid DJ, Frank TS, Soderberg CL, Sitta DL et al (2001) Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst 93(21):1633–1637

    Article  CAS  PubMed  Google Scholar 

  11. Kauff ND, Domchek SM, Friebel TM, Robson ME, Lee J, Garber JE et al (2008) Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol 26(8):1331–1337. https://doi.org/10.1200/JCO.2007.13.9626. PubMed PMID: 18268356; PubMed Central PMCID: PMCPMC3306809

    Article  PubMed  Google Scholar 

  12. Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C et al (2010) Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 304(9):967–975. https://doi.org/10.1001/jama.2010.1237. PubMed PMID: 20810374; PubMed Central PMCID: PMCPMC2948529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ben David Y, Chetrit A, Hirsh-Yechezkel G, Friedman E, Beck BD, Beller U et al (2002) Effect of BRCA mutations on the length of survival in epithelial ovarian tumors. J Clin Oncol 20(2):463–466. https://doi.org/10.1200/JCO.2002.20.2.463

    Article  CAS  PubMed  Google Scholar 

  14. Golan T, Kanji ZS, Epelbaum R, Devaud N, Dagan E, Holter S et al (2014) Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers. Br J Cancer 111(6):1132–1138. https://doi.org/10.1038/bjc.2014.418. PubMed PMID: 25072261; PubMed Central PMCID: PMCPMC4453851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Pomerantz MM, Spisak S, Jia L, Cronin AM, Csabai I, Ledet E et al (2017) The association between germline BRCA2 variants and sensitivity to platinum-based chemotherapy among men with metastatic prostate cancer. Cancer 123:3532–3539. https://doi.org/10.1002/cncr.30808

    Article  CAS  PubMed  Google Scholar 

  16. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M et al (2009) Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 361(2):123–134. https://doi.org/10.1056/NEJMoa0900212

    Article  CAS  PubMed  Google Scholar 

  17. Fong PC, Yap TA, Boss DS, Carden CP, Mergui-Roelvink M, Gourley C et al (2010) Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. J Clin Oncol 28(15):2512–2519. https://doi.org/10.1200/JCO.2009.26.9589

    Article  CAS  PubMed  Google Scholar 

  18. Jarvinen HJ, Aarnio M, Mustonen H, Aktan-Collan K, Aaltonen LA, Peltomaki P et al (2000) Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 118(5):829–834

    Article  CAS  PubMed  Google Scholar 

  19. Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM et al (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349(3):247–257. https://doi.org/10.1056/NEJMoa022289. PubMed PMID: 12867608; PubMed Central PMCID: PMCPMC3584639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Riley BD, Culver JO, Skrzynia C, Senter LA, Peters JA, Costalas JW et al (2012) Essential elements of genetic cancer risk assessment, counseling, and testing: updated recommendations of the National Society of genetic counselors. J Genet Couns 21(2):151–161. https://doi.org/10.1007/s10897-011-9462-x

    Article  PubMed  Google Scholar 

  21. Ladabaum U, Wang G, Terdiman J, Blanco A, Kuppermann M, Boland CR et al (2011) Strategies to identify the Lynch syndrome among patients with colorectal cancer: a cost-effectiveness analysis. Ann Intern Med 155(2):69–79. https://doi.org/10.7326/0003-4819-155-2-201107190-00002. PubMed PMID: 21768580; PubMed Central PMCID: PMCPMC3793257

    Article  PubMed  PubMed Central  Google Scholar 

  22. (1996) Statement of the American Society of Clinical Oncology: genetic testing for cancer susceptibility, Adopted on February 20, 1996. J Clin Oncol 14(5):1730–1736. discussion 7–40

    Google Scholar 

  23. Daly MB, Axilbund JE, Buys S, Crawford B, Farrell CD, Friedman S et al (2010) Genetic/familial high-risk assessment: breast and ovarian. J Natl Compr Cancer Netw 8(5):562–594

    Article  CAS  Google Scholar 

  24. Robson ME, Bradbury AR, Arun B, Domchek SM, Ford JM, Hampel HL et al (2015) American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol 33(31):3660–3667. https://doi.org/10.1200/JCO.2015.63.0996

    Article  CAS  PubMed  Google Scholar 

  25. Trepanier A, Ahrens M, McKinnon W, Peters J, Stopfer J, Grumet SC et al (2004) Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors. J Genet Couns 13(2):83–114. https://doi.org/10.1023/B:JOGC.0000018821.48330.77

    Article  PubMed  Google Scholar 

  26. Association for Molecular Pathology et al v. Myriad Genetics Inc et al (2013) Supreme Court of the United States

    Google Scholar 

  27. Cook-Deegan R, Niehaus A (2014) After myriad: genetic testing in the wake of recent supreme court decisions about gene patents. Curr Genet Med Rep 2(4):223–241. https://doi.org/10.1007/s40142-014-0055-5. PubMed PMID: 25401053; PubMed Central PMCID: PMCPMC4225052

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kurian AW, Hare EE, Mills MA, Kingham KE, McPherson L, Whittemore AS et al (2014) Clinical evaluation of a multiple-gene sequencing panel for hereditary cancer risk assessment. J Clin Oncol 32(19):2001–2009. https://doi.org/10.1200/JCO.2013.53.6607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Walsh T, Casadei S, Lee MK, Pennil CC, Nord AS, Thornton AM et al (2011) Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A 108(44):18032–18037. https://doi.org/10.1073/pnas.1115052108

    Article  PubMed  PubMed Central  Google Scholar 

  30. Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P et al (2015) Identification of a variety of mutations in cancer predisposition genes in patients with suspected Lynch syndrome. Gastroenterology 149(3):604–13 e20. https://doi.org/10.1053/j.gastro.2015.05.006

    Article  CAS  PubMed  Google Scholar 

  31. Pearlman R, Frankel WL, Swanson B, Zhao W, Yilmaz A, Miller K et al (2016) Prevalence and Spectrum of germline cancer susceptibility gene mutations among patients with early-onset colorectal cancer. JAMA Oncol 3:464. https://doi.org/10.1001/jamaoncol.2016.5194

    Article  Google Scholar 

  32. Grant RC, Selander I, Connor AA, Selvarajah S, Borgida A, Briollais L et al (2015) Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer. Gastroenterology 148(3):556–564. https://doi.org/10.1053/j.gastro.2014.11.042

    Article  CAS  PubMed  Google Scholar 

  33. Roychowdhury S, Iyer MK, Robinson DR, Lonigro RJ, Wu YM, Cao X et al (2011) Personalized oncology through integrative high-throughput sequencing: a pilot study. Sci Transl Med 3(111):111ra21. https://doi.org/10.1126/scitranslmed.3003161

    Article  CAS  Google Scholar 

  34. Garraway LA, Lander ES (2013) Lessons from the cancer genome. Cell 153(1):17–37. https://doi.org/10.1016/j.cell.2013.03.002

    Article  CAS  PubMed  Google Scholar 

  35. LaDuca H, Stuenkel AJ, Dolinsky JS, Keiles S, Tandy S, Pesaran T et al (2014) Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients. Genet Med 16(11):830–837. https://doi.org/10.1038/gim.2014.40. PubMed PMID: 24763289; PubMed Central PMCID: PMCPMC4225457

    Article  PubMed  PubMed Central  Google Scholar 

  36. Lowstuter KEC, Sturgeon D, Ricker C, Karam R, LaDuca H, Culver JO, Chao E, Sturgeon J, Speare V, Ma Y, Kingham K, Melas M, Idos GE, McDonnell KJ, Gruber SB (2017) Unexpected CDH1 mutations identified on multigene panels pose clinical management challenges. Precis Oncol 1:1–12. https://doi.org/10.1200/PO.16.00021

    Article  Google Scholar 

  37. Yurgelun MB, Masciari S, Joshi VA, Mercado RC, Lindor NM, Gallinger S et al (2015) Germline TP53 mutations in patients with early-onset colorectal cancer in the colon cancer family registry. JAMA Oncol 1(2):214–221. https://doi.org/10.1001/jamaoncol.2015.0197. PubMed PMID: 26086041; PubMed Central PMCID: PMCPMC4465271

    Article  PubMed  Google Scholar 

  38. Whitworth J, Skytte AB, Sunde L, Lim DH, Arends MJ, Happerfield L et al (2016) Multilocus inherited neoplasia alleles syndrome: a case series and review. JAMA Oncol 2(3):373–379. https://doi.org/10.1001/jamaoncol.2015.4771

    Article  PubMed  Google Scholar 

  39. Domchek SM, Bradbury A, Garber JE, Offit K, Robson ME (2013) Multiplex genetic testing for cancer susceptibility: out on the high wire without a net? J Clin Oncol 31(10):1267–1270. https://doi.org/10.1200/JCO.2012.46.9403

    Article  PubMed  Google Scholar 

  40. Bombard Y, Robson M, Offit K (2013) Revealing the incidentalome when targeting the tumor genome. JAMA 310(8):795–796. https://doi.org/10.1001/jama.2013.276573. Epub 2013/08/29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Stadler ZK, Schrader KA, Vijai J, Robson ME, Offit K (2014) Cancer genomics and inherited risk. J Clin Oncol 32(7):687–698. https://doi.org/10.1200/JCO.2013.49.7271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Raymond VM, Gray SW, Roychowdhury S, Joffe S, Chinnaiyan AM, Parsons DW et al (2016) Germline findings in tumor-only sequencing: points to consider for clinicians and laboratories. J Natl Cancer Inst 108:4. https://doi.org/10.1093/jnci/djv351

    Article  CAS  Google Scholar 

  43. Catenacci DV, Amico AL, Nielsen SM, Geynisman DM, Rambo B, Carey GB et al (2015) Tumor genome analysis includes germline genome: are we ready for surprises? Int J Cancer 136(7):1559–1567. https://doi.org/10.1002/ijc.29128

    Article  CAS  PubMed  Google Scholar 

  44. Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL et al (2013) ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med 15(7):565–574.. Epub 2013/06/22. https://doi.org/10.1038/gim.2013.73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C, Evans JP et al (2016) Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med 19:249–255. https://doi.org/10.1038/gim.2016.190

    Article  PubMed  Google Scholar 

  46. Burke W, Antommaria AH, Bennett R, Botkin J, Clayton EW, Henderson GE et al (2013) Recommendations for returning genomic incidental findings? We need to talk! Genet Med 15(11):854–859. https://doi.org/10.1038/gim.2013.113

    Article  CAS  PubMed  Google Scholar 

  47. Parsons DW, Roy A, Plon SE, Roychowdhury S, Chinnaiyan AM (2014) Clinical tumor sequencing: an incidental casualty of the American College of Medical Genetics and Genomics recommendations for reporting of incidental findings. J Clin Oncol 32(21):2203–2205. https://doi.org/10.1200/JCO.2013.54.8917

    Article  PubMed  PubMed Central  Google Scholar 

  48. Schrader KA, Cheng DT, Joseph V, Prasad M, Walsh M, Zehir A et al (2016) Germline variants in targeted tumor sequencing using matched Normal DNA. JAMA Oncol 2(1):104–111. https://doi.org/10.1001/jamaoncol.2015.5208

    Article  PubMed  PubMed Central  Google Scholar 

  49. Seifert BA, O’Daniel JM, Amin K, Marchuk DS, Patel NM, Parker JS et al (2016) Germline analysis from tumor-germline sequencing dyads to identify clinically actionable secondary findings. Clin Cancer Res 22(16):4087–4094. https://doi.org/10.1158/1078-0432.CCR-16-0015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Meric-Bernstam F, Brusco L, Daniels M, Wathoo C, Bailey AM, Strong L et al (2016) Incidental germline variants in 1000 advanced cancers on a prospective somatic genomic profiling protocol. Ann Oncol 27(5):795–800. https://doi.org/10.1093/annonc/mdw018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM et al (2015) Integrative clinical genomics of advanced prostate cancer. Cell 161(5):1215–1228. https://doi.org/10.1016/j.cell.2015.05.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Robinson DR, Wu Y, Lonigro RJ, Vat P, Cobain E, Everett J et al (2017) Integrative clinical genomics of metastatic cancer. Nature 548:297–303. https://doi.org/10.1038/nature23306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Mody RJ, Wu YM, Lonigro RJ, Cao X, Roychowdhury S, Vats P et al (2015) Integrative clinical sequencing in the Management of Refractory or relapsed cancer in youth. JAMA 314(9):913–925. https://doi.org/10.1001/jama.2015.10080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Parsons DW, Roy A, Yang Y, Wang T, Scollon S, Bergstrom K et al (2016) Diagnostic yield of clinical tumor and germline whole-exome sequencing for children with solid tumors. JAMA Oncol 2:616. https://doi.org/10.1001/jamaoncol.2015.5699

    Article  PubMed  PubMed Central  Google Scholar 

  55. Zhang J, Walsh MF, Wu G, Edmonson MN, Gruber TA, Easton J et al (2015) Germline mutations in predisposition genes in pediatric cancer. N Engl J Med 373(24):2336–2346. https://doi.org/10.1056/NEJMoa1508054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Tomlinson AN, Skinner D, Perry DL, Scollon SR, Roche MI, Bernhardt BA (2016) “Not tied up neatly with a bow”: professionals’ challenging cases in informed consent for genomic sequencing. J Genet Couns 25(1):62–72. https://doi.org/10.1007/s10897-015-9842-8

    Article  PubMed  Google Scholar 

  57. ABo D (2015) ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing. Genet Med 17(1):68–69. https://doi.org/10.1038/gim.2014.151

    Article  Google Scholar 

  58. Everett JN, Gustafson SL, Raymond VM (2014) Traditional roles in a non-traditional setting: genetic counseling in precision oncology. J Genet Couns 23(4):655–660. https://doi.org/10.1007/s10897-014-9698-3

    Article  PubMed  PubMed Central  Google Scholar 

  59. Gray SW, Park ER, Najita J, Martins Y, Traeger L, Bair E et al (2016) Oncologists‘ and cancer patients’ views on whole-exome sequencing and incidental findings: results from the CanSeq study. Genet Med 18(10):1011–1019. https://doi.org/10.1038/gim.2015.207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hooker GW, Ormond KE, Sweet K, Biesecker BB (2014) Teaching genomic counseling: preparing the genetic counseling workforce for the genomic era. J Genet Couns 23(4):445–451. https://doi.org/10.1007/s10897-014-9689-4

    Article  PubMed  PubMed Central  Google Scholar 

  61. Bernhardt BA, Roche MI, Perry DL, Scollon SR, Tomlinson AN, Skinner D (2015.;167A) Experiences with obtaining informed consent for genomic sequencing. Am J Med Genet A 167(11):2635–2646. https://doi.org/10.1002/ajmg.a.37256

    Article  Google Scholar 

  62. Scollon S, Bergstrom K, Kerstein RA, Wang T, Hilsenbeck SG, Ramamurthy U et al (2014) Obtaining informed consent for clinical tumor and germline exome sequencing of newly diagnosed childhood cancer patients. Genome Med 6(9):69. https://doi.org/10.1186/s13073-014-0069-3

    Article  PubMed  PubMed Central  Google Scholar 

  63. Cohen SA, Marvin ML, Riley BD, Vig HS, Rousseau JA, Gustafson SL (2013) Identification of genetic counseling service delivery models in practice: a report from the NSGC Service delivery model task force. J Genet Couns 22(4):411–421. https://doi.org/10.1007/s10897-013-9588-0

    Article  PubMed  Google Scholar 

  64. Cohen SA, Huziak RC, Gustafson S, Grubs RE (2016) Analysis of advantages, limitations, and barriers of genetic counseling service delivery models. J Genet Couns 25(5):1010–1018. https://doi.org/10.1007/s10897-016-9932-2

    Article  PubMed  Google Scholar 

  65. Vig HS, Wang C (2012) The evolution of personalized cancer genetic counseling in the era of personalized medicine. Familial Cancer 11(3):539–544. https://doi.org/10.1007/s10689-012-9524-8. PubMed PMID: 22419176; PubMed Central PMCID: PMCPMC3905734

    Article  PubMed  PubMed Central  Google Scholar 

  66. Cohen SA, McIlvried D, Schnieders J (2009) A collaborative approach to genetic testing: a community hospital’s experience. J Genet Couns 18(6):530–533. https://doi.org/10.1007/s10897-009-9243-y

    Article  PubMed  Google Scholar 

  67. Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H et al (2016) Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med 375(5):443–453. https://doi.org/10.1056/NEJMoa1603144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Hu C, Hart SN, Bamlet WR, Moore RM, Nandakumar K, Eckloff BW et al (2016) Prevalence of pathogenic mutations in cancer predisposition genes among pancreatic cancer patients. Cancer Epidemiol Biomark Prev 25(1):207–211. https://doi.org/10.1158/1055-9965.EPI-15-0455

    Article  CAS  Google Scholar 

  69. Antoniou AC, Casadei S, Heikkinen T, Barrowdale D, Pylkas K, Roberts J et al (2014) Breast-cancer risk in families with mutations in PALB2. N Engl J Med 371(6):497–506. https://doi.org/10.1056/NEJMoa1400382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Moran O, Nikitina D, Royer R, Poll A, Metcalfe K, Narod SA et al (2017) Revisiting breast cancer patients who previously tested negative for BRCA mutations using a 12-gene panel. Breast Cancer Res Treat 161(1):135–142. https://doi.org/10.1007/s10549-016-4038-y

    Article  CAS  PubMed  Google Scholar 

  71. Yadav S, Reeves A, Campian S, Paine A, Zakalik D (2017) Outcomes of retesting BRCA negative patients using multigene panels. Familial Cancer 16(3):319–328. https://doi.org/10.1007/s10689-016-9956-7

    Article  PubMed  Google Scholar 

  72. Otten E, Plantinga M, Birnie E, Verkerk MA, Lucassen AM, Ranchor AV et al (2015) Is there a duty to recontact in light of new genetic technologies? A systematic review of the literature. Genet Med 17(8):668–678. https://doi.org/10.1038/gim.2014.173

    Article  CAS  PubMed  Google Scholar 

  73. Daly MB, Pilarski R, Axilbund JE, Berry M, Buys SS, Crawford B et al (2016) Genetic/familial high-risk assessment: breast and ovarian, version 2.2015. J Natl Compr Cancer Netw 14(2):153–162

    Article  Google Scholar 

  74. King MC, Levy-Lahad E, Lahad A (2014) Population-based screening for BRCA1 and BRCA2: 2014 Lasker award. JAMA 312(11):1091–1092. https://doi.org/10.1001/jama.2014.12483

    Article  CAS  PubMed  Google Scholar 

  75. Win AK, Lindor NM, Jenkins MA (2013) Risk of breast cancer in Lynch syndrome: a systematic review. Breast Cancer Res 15(2):R27. https://doi.org/10.1186/bcr3405. PubMed PMID: 23510156; PubMed Central PMCID: PMCPMC3672741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Harkness EF, Barrow E, Newton K, Green K, Clancy T, Lalloo F et al (2015) Lynch syndrome caused by MLH1 mutations is associated with an increased risk of breast cancer: a cohort study. J Med Genet 52(8):553–556. https://doi.org/10.1136/jmedgenet-2015-103216. PubMed PMID: 26101330

    Article  CAS  PubMed  Google Scholar 

  77. Wood ME, Kadlubek P, Pham TH, Wollins DS, Lu KH, Weitzel JN et al (2014) Quality of cancer family history and referral for genetic counseling and testing among oncology practices: a pilot test of quality measures as part of the american society of clinical oncology quality oncology practice initiative. J Clin Oncol 32(8):824–829. Epub 2014/02/05. https://doi.org/10.1200/JCO.2013.51.4661

    Article  PubMed  PubMed Central  Google Scholar 

  78. Weitzel JN, Lagos VI, Cullinane CA, Gambol PJ, Culver JO, Blazer KR et al (2007) Limited family structure and BRCA gene mutation status in single cases of breast cancer. JAMA 297(23):2587–2595. https://doi.org/10.1001/jama.297.23.2587. PubMed PMID: 17579227

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. New York University, New York, NY, USA

    Jessica N. Everett & Victoria M. Raymond

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  1. Jessica N. Everett
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  2. Victoria M. Raymond
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Correspondence to Jessica N. Everett .

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Editors and Affiliations

  1. Department of Internal Medicine, Division of Medical Oncology Comprehensive Cancer Center & The Arthur G. James Cancer Hospital at The Ohio State University, Columbus, OH, USA

    Sameek Roychowdhury

  2. Dana-Farber Cancer Institute, Boston, MA, USA

    Eliezer M. Van Allen

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Everett, J.N., Raymond, V.M. (2019). Managing Germline Findings from Molecular Testing in Precision Oncology. In: Roychowdhury, S., Van Allen, E. (eds) Precision Cancer Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-23637-3_8

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