Multigene Cancer Panels: Implications for Pre- and Post-test Genetic Counseling

  • Margo C. Grady
  • Kavitha A. Kolla
  • Beth N. PeshkinEmail author
Counseling and Testing (C Reiser and C Walton, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Counseling and Testing


Purpose of Review

The availability of multigene cancer panel testing (MCPT) has revolutionized the care of individuals and families at risk for hereditary cancer. This review discusses fundamental components of genetic counseling, test selection, result interpretation, and follow-up related to MCPT.

Recent Findings

Routine use of MCPT increases the diagnostic yield for major hereditary cancers such as breast, ovarian, and colon, with the identification of pathogenic variants in high- and moderate-penetrance genes. In addition, the larger the panel, the more likely one or more variants of uncertain significance will be identified. Furthermore, although index cases who test negative after multigene panel testing may derive some reassurance about hereditary risk, assessment and management based on personal and family history are the keys.


Given the complexity of MCPT, pre- and post-test genetic counseling approaches have been adapted to optimize the delivery of information and support to patients and their families.


Cancer genetics Genetic counseling Multigene cancer panels Cancer genetic testing 



The authors are grateful to Savannah Binion, BA, for assistance with manuscript preparation and editing.

Compliance with Ethical Standards

Conflict of Interest

Ms. Kolla declares no conflicts of interest.

Ms. Grady reports consulting fees from ActX (Seattle, WA).

Ms. Peshkin reports consulting fees from Clear Genetics, Inc. (San Francisco, CA).

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Phillips KA, Deverka PA, Hooker GW, Douglas MP. Genetic test availability and spending: where are we now? Where are we going? Health Aff (Millwood). 2018;37:710–6. Scholar
  2. 2.
    Narod SA, Foulkes WD. BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer. 2004;4:665–76. Scholar
  3. 3.
    Lynch HT, Snyder CL, Shaw TG, Heinen CD, Hitchins MP. Milestones of Lynch syndrome: 1895–2015. Nat Rev Cancer. 2015;15:181–94. Scholar
  4. 4.
    •• Hooker GW, Clemens KR, Quillin J, Vogel Postula KJ, Summerour P, Nagy R, et al. Cancer genetic counseling and testing in an era of rapid change. J Genet Couns. 2017;26:1244–53. The authors report the results of a survey of genetic counselors regarding their use of multigene panel testing after patents on the BRCA genes were lifted in 2013. CrossRefPubMedGoogle Scholar
  5. 5.
    Kurian AW, Ward KC, Hamilton AS, Deapen DM, Abrahamse P, Bondarenko I, et al. Uptake, results, and outcomes of germline multiple-gene sequencing after diagnosis of breast cancer. JAMA Oncol. 2018;4:1066–72. Scholar
  6. 6.
    • Bradbury AR, Patrick-Miller L, Long J, Powers J, Stopfer J, Forman A, et al. Development of a tiered and binned genetic counseling model for informed consent in the era of multiplex testing for cancer susceptibility. Genet Med. 2015;17:485–92. This paper describes the development of a new model of genetic counseling for patients undergoing multigene panel testing. CrossRefPubMedGoogle Scholar
  7. 7.
    Domchek SM, Bradbury A, Garber JE, Offit K, Robson ME. Multiplex genetic testing for cancer susceptibility: out on the high wire without a net? J Clin Oncol. 2013;31:1267–70. Scholar
  8. 8.
    Lundy MG, Forman A, Valverde K, Kessler L. An investigation of genetic counselors’ testing recommendations: pedigree analysis and the use of multiplex breast cancer panel testing. J Genet Couns. 2014;23:618–32. Scholar
  9. 9.
    Esteban I, Lopez-Fernandez A, Balmaña J. A narrative overview of the patients’ outcomes after multigene cancer panel testing, and a thorough evaluation of its implications for genetic counselling. Eur J Med Genet. 2019;62:342–9. Scholar
  10. 10.
    Berliner JL, Fay AM, Cummings SA, Burnett B, Tillmanns T. NSGC practice guideline: risk assessment and genetic counseling for hereditary breast and ovarian cancer. J Genet Couns. 2013;22:155–63. Scholar
  11. 11.
    Forman A, Schwartz S. Guidelines-based cancer risk assessment. Semin Oncol Nurs. 2019;35:34–46. Scholar
  12. 12.
    Powers J, Stopfer JE. Risk assessment, genetic counseling, and clinical care for hereditary breast cancer. J Obstet Gynecol Neonatal Nurs. 2014;43:361–73. Scholar
  13. 13.
    •• Daly MB, Pilarski R, Berry MP, Buys SS, Friedman S, Garber JE, et al. Genetic/familial high-risk assessment: breast and ovarian. NCCN [Internet]. 2019; Version 3. Available from: Accessed 03 Sept 2019. National guidelines about the identification and management of individuals with or at risk for hereditary breast and ovarian cancer.
  14. 14.
    •• Provenzale D, Gupta S, Ahnen DJ, Blanco AM, Bray TH, Chung DC, et al. Genetic/familial high-risk assessment: colorectal. NCCN [Internet]. 2019; Version 1. Available from: Accessed 03 Sept 2019. National guidelines about the identification and management of individuals with or at risk for hereditary colorectal cancer.
  15. 15.
    Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL. Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015;17:70–87. Scholar
  16. 16.
    Bradbury AR, Patrick-Miller L, Domchek S. Multiplex genetic testing: reconsidering utility and informed consent in the era of next-generation sequencing. Genet Med. 2014;17:97–8. Scholar
  17. 17.
    Flores KG, Steffen LE, McLouth CJ, Vicuña BE, Gammon A, Kohlmann W, et al. Factors associated with interest in gene-panel testing and risk communication preferences in women from BRCA1/2 negative families. J Genet Couns. 2017;26:480–90. Scholar
  18. 18.
    Fecteau H, Vogel KJ, Hanson K, Morrill-Cornelius S. The evolution of cancer risk assessment in the era of next generation sequencing. J Genet Couns. 2014;23:633–9. Scholar
  19. 19.
    Couch FJ, Shimelis H, Hu C, Hart SN, Polley EC, Na J, et al. Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol. 2017;3:1190–6. Scholar
  20. 20.
    Easton DF, Pharoah PDP, Antoniou AC, Tischkowitz M, Tavtigian SV, Nathanson KL, et al. Gene-panel sequencing and the prediction of breast-cancer risk. N Engl J Med. 2015;372:2243–57. Scholar
  21. 21.
    Kurian AW, Antoniou AC, Domchek SM. Refining breast cancer risk stratification: additional genes, additional information. Am Soc Clin Oncol Educ Book. 2016:44–56.
  22. 22.
    •• Tung N, Domchek SM, Stadler Z, Nathanson KL, Couch F, Garber JE, et al. Counselling framework for moderate-penetrance cancer-susceptibility mutations. Nat Rev Clin Oncol. 2016;13:581–8. This paper describes the counseling framework for cancer risks high- vs. moderate-risk genes and management considerations for moderate risk cancer genes. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Bonadona V, Bonaïti B, Olschwang S, Grandjouan S, Huiart L, Longy M, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011;305:2304–10. Scholar
  24. 24.
    Hall MJ, Obeid EI, Schwartz SC, Mantia-Smaldone G, Forman AD, Daly MB. Genetic testing for hereditary cancer predisposition: BRCA1/2, Lynch syndrome, and beyond. Gynecol Oncol. 2016;140:565–74. Scholar
  25. 25.
    Lorans M, Dow E, Macrae FA, Winship IM, Buchanan DD. Update on hereditary colorectal cancer: improving the clinical utility of multigene panel testing. Clin Colorectal Cancer. 2018;17:e293–305. Scholar
  26. 26.
    Lu H-M, Li S, Black MH, Lee S, Hoiness R, Wu S, et al. Association of breast and ovarian cancers with predisposition genes identified by large-scale sequencing. JAMA Oncol. 2018.
  27. 27.
    Giri VN, Hegarty SE, Hyatt C, O’Leary E, Garcia J, Knudsen KE, et al. Germline genetic testing for inherited prostate cancer in practice: implications for genetic testing, precision therapy, and cascade testing. Prostate. 2019;79:333–9. Scholar
  28. 28.
    •• Lee K, Seifert BA, Shimelis H, Ghosh R, Crowley SB, Carter NJ, et al. Clinical validity assessment of genes frequently tested on hereditary breast and ovarian cancer susceptibility sequencing panels. Genet Med. 2019;21:1479–506. This paper evaluates gene-disease association for 31 genes commonly offered on multigene cancer panel tests. CrossRefGoogle Scholar
  29. 29.
    •• Rosenthal ET, Bernhisel R, Brown K, Kidd J, Manley S. Clinical testing with a panel of 25 genes associated with increased cancer risk results in a significant increase in clinically significant findings across a broad range of cancer histories. Cancer Genet. 2017;218–219:58–68. This study reports on the outcome of a broad 25-gene cancer panel test in a consecutive series of 252,223 individuals. CrossRefPubMedGoogle Scholar
  30. 30.
    •• Mersch J, Brown N, Pirzadeh-Miller S, Mundt E, Cox HC, Brown K, et al. Prevalence of variant reclassification following hereditary cancer genetic testing. JAMA. 2018;320:1266–74. The authors found that of 2048 reclassified variants, over 91% of were downgraded to benign or likely benign and 8.7% were upgraded to pathogenic or likely pathogenic. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Slavin TP, Van Tongeren LR, Behrendt CE, Solomon I, Rybak C, Nehoray B, et al. Prospective study of cancer genetic variants: variation in rate of reclassification by ancestry. J Natl Cancer Inst. 2018;110:1059–66. Scholar
  32. 32.
    Szender JB, Kaur J, Clayback K, Hutton ML, Mikkelson J, Odunsi K, et al. Breadth of genetic testing selected by patients at risk of hereditary breast and ovarian cancer. Int J Gynecol Cancer. 2018;28:26–33. Scholar
  33. 33.
    Domchek SM. Risk-reducing mastectomy in BRCA1 and BRCA2 mutation carriers: a complex discussion. JAMA. 2019;321:27. Scholar
  34. 34.
    Finch APM, Lubinski J, Møller P, Singer CF, Karlan B, Senter L, et al. Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. J Clin Oncol. 2014;32:1547–53. Scholar
  35. 35.
    De Vos Tot Nederveen Cappel WH, Järvinen HJ, Lynch PM, Engel C, Mecklin J-P, Vasen HFA. Colorectal surveillance in Lynch syndrome families. Familial Cancer. 2013;12:261–5. Scholar
  36. 36.
    Henn J, Spier I, Adam RS, Holzapfel S, Uhlhaas S, Kayser K, et al. Diagnostic yield and clinical utility of a comprehensive gene panel for hereditary tumor syndromes. Hered Cancer Clin Pract. 2019;17:5. Scholar
  37. 37.
    •• O’Leary E, Iacoboni D, Holle J, Michalski ST, Esplin ED, Yang S, et al. Expanded gene panel use for women with breast cancer: identification and intervention beyond breast cancer risk. Ann Surg Oncol. 2017;24:3060–6. This study reports on clinician ordering patterns for MCPT and increasing diagnostic and clinical yield with broader panel testing. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Ricker C, Culver JO, Lowstuter K, Sturgeon D, Sturgeon JD, Chanock CR, et al. Increased yield of actionable mutations using multi-gene panels to assess hereditary cancer susceptibility in an ethnically diverse clinical cohort. Cancer Gene Ther. 2016;209:130–7. Scholar
  39. 39.
    •• Susswein LR, Marshall ML, Nusbaum R, Vogel Postula KJ, Weissman SM, Yackowski L, et al. Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. Genet Med. 2016;18:823–32. This study reviewed results on 10,000 patients tested by MGPT and found that individuals often had PVs identified in genes not consistent with family history. CrossRefPubMedGoogle Scholar
  40. 40.
    Genetic Testing Registry (GTR) - NCBI [Internet]. [cited 2019]. Available from: Accessed 03 Sept 2019.
  41. 41.
    Robson ME, Bradbury AR, Arun B, Domchek SM, Ford JM, Hampel HL, et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. JCO. 2015;33:3660–7. Scholar
  42. 42.
    Medendorp NM, Hillen MA, Murugesu L, Aalfs CM, Stiggelbout AM, Smets EMA. Uncertainty in consultations about genetic testing for cancer: an explorative observational study. Patient Educ Couns. 2018;101:2083–9. Scholar
  43. 43.
    Courtney E, Li S-T, Shaw T, Chen Y, Allen JC, Ngeow J. Predictors of next-generation sequencing panel selection using a shared decision-making approach. NPJ Genom Med. 2018;3:11. Scholar
  44. 44.
    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:e72–8. Scholar
  45. 45.
    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.
  46. 46.
    Thompson ER, Rowley SM, Li N, McInerny S, Devereux L, Wong-Brown MW, et al. Panel testing for familial breast cancer: calibrating the tension between research and clinical care. JCO. 2016;34:1455–9. Scholar
  47. 47.
    LaDuca H, Stuenkel AJ, Dolinsky JS, Keiles S, Tandy S, Pesaran T, et al. Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients. Genet Med. 2014;16:830–7. Scholar
  48. 48.
    Desmond A, Kurian AW, Gabree M, Mills MA, Anderson MJ, Kobayashi Y, et al. Clinical actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment. JAMA Oncol. 2015;1:943–51. Scholar
  49. 49.
    Medendorp NM, Hillen MA, Murugesu L, Aalfs CM, Stiggelbout AM, Smets EMA. Uncertainty related to multigene panel testing for cancer: a qualitative study on counsellors’ and counselees’ views. J Community Genet. 2019;10:303–12. Scholar
  50. 50.
    Bijlsma RM, Wouters RHP, Wessels H, May AM, Ausems MGEM, Voest EE, et al. Managing unsolicited findings in genomics: a qualitative interview study with cancer patients. Psychooncology. 2018;27:1327–33. Scholar
  51. 51.
    Bijlsma RM, Wessels H, Wouters RHP, May AM, Ausems MGEM, Voest EE, et al. Cancer patients’ intentions towards receiving unsolicited genetic information obtained using next-generation sequencing. Familial Cancer. 2018;17:309–16. Scholar
  52. 52.
    Kaphingst KA, Ivanovich J, Lyons S, Biesecker B, Dresser R, Elrick A, et al. Preferences for learning different types of genome sequencing results among young breast cancer patients: role of psychological and clinical factors. Transl Behav Med. 2018;8:71–9. Scholar
  53. 53.
    Lumish HS, Steinfeld H, Koval C, Russo D, Levinson E, Wynn J, et al. Impact of panel gene testing for hereditary breast and ovarian cancer on patients. J Genet Couns. 2017;26:1116–29. Scholar
  54. 54.
    Shannon KM, Rodgers LH, Chan-Smutko G, Patel D, Gabree M, Ryan PD. Which individuals undergoing BRACAnalysis need BART testing? Cancer Gene Ther. 2011;204:416–22. Scholar
  55. 55.
    Menko FH, ter Stege JA, van der Kolk LE, Jeanson KN, Schats W, Moha DA, et al. The uptake of presymptomatic genetic testing in hereditary breast-ovarian cancer and Lynch syndrome: a systematic review of the literature and implications for clinical practice. Familial Cancer. 2019;18:127–35. Scholar
  56. 56.
    Hampel H. Genetic counseling and cascade genetic testing in Lynch syndrome. Familial Cancer. 2016;15:423–7. Scholar
  57. 57.
    Thomas MH, Higgs LK, Modesitt SC, Schroen AT, Ring KL, Dillon PM. Cases and evidence for panel testing in cancer genetics: is site-specific testing dead? J Genet Couns. 2019;28:700–7. Scholar
  58. 58.
    •• Caswell-Jin JL, Gupta T, Hall E, Petrovchich IM, Mills MA, Kingham KE, et al. Racial/ethnic differences in multiple-gene sequencing results for hereditary cancer risk. Genet Med. 2018;20:234–9. This paper reports on using a panel for cascade testing and the frequency of identifying a PV other than the familial mutation. CrossRefPubMedGoogle Scholar
  59. 59.
    Meric-Bernstam F, Brusco L, Daniels M, Wathoo C, Bailey AM, Strong L, et al. Incidental germline variants in 1000 advanced cancers on a prospective somatic genomic profiling protocol. Ann Oncol. 2016;27:795–800. Scholar
  60. 60.
    Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, et al. Standards and guidelines for the interpretation and reporting of sequence variants in cancer: a joint consensus recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn. 2017;19:4–23. Scholar
  61. 61.
    Haque MM, Kowtal P, Sarin R. Identification and characterization of TP53 gene allele dropout in Li-Fraumeni syndrome and oral cancer cohorts. Sci Rep. 2018;8:11705. Scholar
  62. 62.
    •• Brown S, Puumala S, Leonhard J, Bell M, Flanagan J, Dean LW, et al. Genesurance counseling: genetic counselors’ roles and responsibilities in regards to genetic insurance and financial topics. J Genet Couns. 2018;27:800–13. This study reports on “genesurance counseling” and how genetic counselors cover insurance information into pre-test genetic counseling. CrossRefPubMedGoogle Scholar
  63. 63.
    Wagner C, Murphy L, Harkenrider J, Darilek S, Soto-Torres E, Stein Q, et al. Genesurance counseling: patient perspectives. J Genet Couns. 2018;27:814–22. Scholar
  64. 64.
    Walcott FL, Dunn BK. Legislation in the genomic era: the Affordable Care Act and genetic testing for cancer risk assessment. Genet Med. 2015;17:962–4. Scholar
  65. 65.
    Clain E, Trosman JR, Douglas MP, Weldon CB, Phillips KA. Availability and payer coverage of BRCA1/2 tests and gene panels. Nat Biotechnol. 2015;33:900–2. Scholar
  66. 66.
    Trosman JR, Weldon CB, Douglas MP, Kurian AW, Kelley RK, Deverka PA, et al. Payer coverage for hereditary cancer panels: barriers, opportunities, and implications for the precision medicine initiative. J Natl Compr Cancer Netw. 2017;15:219–28. Scholar
  67. 67.
    Prince AER, Roche MI. Genetic information, non-discrimination, and privacy protections in genetic counseling practice. J Genet Couns. 2014;23:891–902. Scholar
  68. 68.
    Genetic Information Nondiscrimination Act of 2008 [Internet]. [cited 2019]. Available from: Accessed 03 Sept 2019.
  69. 69.
    Genetic Discrimination [Internet]. [cited 2019]. Available from: Accessed 03 Sept 2019.
  70. 70.
    Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW, et al. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;110:223–62; quiz 263. Scholar
  71. 71.
    Boland PM, Yurgelun MB, Boland CR. Recent progress in Lynch syndrome and other familial colorectal cancer syndromes. CA Cancer J Clin. 2018;68:217–31. Scholar
  72. 72.
    Nathan MR, Schmid P. The emerging world of breast cancer immunotherapy. Breast. 2018;37:200–6. Scholar
  73. 73.
    Roberts ME, Ranola JMO, Marshall ML, Susswein LR, Graceffo S, Bohnert K, et al. Comparison of CDH1 penetrance estimates in clinically ascertained families vs families ascertained for multiple gastric cancers. JAMA Oncol. 2019.
  74. 74.
    Van Der Post RS, Vogelaar IP, Carneiro F, Guilford P, Huntsman D, Hoogerbrugge N, et al. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet. 2015;52:361–74. Scholar
  75. 75.
    Hallowell N, Lawton J, Badger S, Richardson S, Hardwick RH, Caldas C, et al. The psychosocial impact of undergoing Prophylactic Total Gastrectomy (PTG) to manage the risk of Hereditary Diffuse Gastric Cancer (HDGC). J Genet Couns. 2017;26:752–62. Scholar
  76. 76.
    •• Lowstuter K, Espenschied CR, Sturgeon D, Ricker C, Karam R, LaDuca H, et al. Unexpected CDH1 mutations identified on multigene panels pose clinical management challenges. JCO Precis Oncol. 2017:1–12. Authors identified carriers of CDH1 and found that 65% of mutation carriers did not meet the revised testing criteria published in 2015. All three CDH1 mutation carriers who had risk-reducing gastrectomy had pathologic evidence of diffuse gastric cancer despite not having met IGCLC criteria.
  77. 77.
    •• Harrison SM, Dolinsky JS, Knight Johnson AE, Pesaran T, Azzariti DR, Bale S, et al. Clinical laboratories collaborate to resolve differences in variant interpretations submitted to ClinVar. Genet Med. 2017;19:1096–104. This study reviewed 6,169 variants in ClinVar, of which 88.3% were initially concordant and reassessed 242/724 initially discordant variants, of which 87.2% (211) were resolved by reassessment with current criteria and/or internal data sharing. CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Garcia C, Lyon L, Littell RD, Powell CB. Comparison of risk management strategies between women testing positive for a BRCA variant of unknown significance and women with known BRCA deleterious mutations. Genet Med. 2014;16:896–902. Scholar
  79. 79.
    Hoffman-Andrews L. The known unknown: the challenges of genetic variants of uncertain significance in clinical practice. J Law Biosci. 2017;4:648–57. Scholar
  80. 80.
    Rhees J, Arnold M, Boland CR. Inversion of exons 1-7 of the MSH2 gene is a frequent cause of unexplained Lynch syndrome in one local population. Familial Cancer. 2014;13:219–25. Scholar
  81. 81.
    •• Girardi F, Barnes DR, Barrowdale D, Frost D, Brady AF, Miller C, et al. Risks of breast or ovarian cancer in BRCA1 or BRCA2 predictive test negatives: findings from the EMBRACE study. Genet Med. 2018;20:1575–82. This study evaluated 1895 unaffected women who did not inherit a familial pathogenic variant in BRCA1/2. No increased risks for breast or ovarian cancer identified. CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Ingham SL, Warwick J, Buchan I, Sahin S, O’Hara C, Moran A, et al. Ovarian cancer among 8,005 women from a breast cancer family history clinic: no increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2. J Med Genet. 2013;50:368–72. Scholar
  83. 83.
    •• Reiner AS, Sisti J, John EM, Lynch CF, Brooks JD, Mellemkjær L, et al. Breast cancer family history and contralateral breast cancer risk in young women: An update from the women’s environmental cancer and radiation epidemiology study. J Clin Oncol. 2018;36:1513–20. This study found that breast cancer family history confers a high risk of contralateral breast cancer, even after excluding women with PVs in breast cancer genes. CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Provenzale D, Gupta S, Ahnen DJ, Chen L-M, Chung DC, Cooper G, et al. Colorectal cancer screening. NCCN [Internet]. 2019;Version 1. Available from: Accessed 03 Sept 2019.
  85. 85.
    Brentnall AR, Cuzick J, Buist DSM, Bowles EJA. Long-term accuracy of breast cancer risk assessment combining classic risk factors and breast density. JAMA Oncol. 2018;4:e180174. Scholar
  86. 86.
    Pruthi S, Heisey RE, Bevers TB. Chemoprevention for breast cancer. Ann Surg Oncol. 2015;22:3230–5. Scholar
  87. 87.
    Lee AJ, Cunningham AP, Tischkowitz M, Simard J, Pharoah PD, Easton DF, et al. Incorporating truncating variants in PALB2, CHEK2, and ATM into the BOADICEA breast cancer risk model. Genet Med. 2016;18:1190–8. Scholar
  88. 88.
    Martin AR, Kanai M, Kamatani Y, Okada Y, Neale BM, Daly MJ. Clinical use of current polygenic risk scores may exacerbate health disparities. Nat Genet. 2019;51:584–91. Scholar
  89. 89.
    Wald NJ, Old R. The illusion of polygenic disease risk prediction. Genet Med. 2019;21:1705–7. Scholar
  90. 90.
    Mets S, Tryon R, Veach PM, Zierhut HA. Genetic counselors’ experiences regarding communication of reproductive risks with autosomal recessive conditions found on cancer panels. J Genet Couns. 2016;25:359–72. Scholar
  91. 91.
    Bradbury AR, Patrick-Miller LJ, Egleston BL, DiGiovanni L, Brower J, Harris D, et al. Patient feedback and early outcome data with a novel tiered-binned model for multiplex breast cancer susceptibility testing. Genet Med. 2016;18:25–33. Scholar
  92. 92.
    Esteban I, Vilaró M, Adrover E, Angulo A, Carrasco E, Gadea N, et al. Psychological impact of multigene cancer panel testing in patients with a clinical suspicion of hereditary cancer across Spain. Psycho-Oncology. 2018;27:1530–7. Scholar
  93. 93.
    Vos J, Otten W, van Asperen C, Jansen A, Menko F, Tibben A. The counsellees’ view of an unclassified variant in BRCA1/2: recall, interpretation, and impact on life. Psycho-Oncology. 2008;17:822–30. Scholar
  94. 94.
    •• Reuter C, Chun N, Pariani M, Hanson-Kahn A. Understanding variants of uncertain significance in the era of multigene panels: through the eyes of the patient. J Genet Couns. 2019. This study used a semi-structured interview on adults who had a VUS identified on a multi-gene panel and found participants understood the lack of clinical significance of a VUS, yet often interpreted the etiologic significance of a VUS within the context of the personal and family history.
  95. 95.
    Giri VN, Obeid E, Hegarty SE, Gross L, Bealin L, Hyatt C, et al. Understanding of multigene test results among males undergoing germline testing for inherited prostate cancer: implications for genetic counseling. Prostate. 2018;78:879–88. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Margo C. Grady
    • 1
  • Kavitha A. Kolla
    • 2
    • 3
  • Beth N. Peshkin
    • 3
    • 4
    Email author
  1. 1.ProHealth CareMilwaukeeUSA
  2. 2.MedStar Georgetown University HospitalGeorgetown Lombardi Comprehensive Cancer CenterWashington, DCUSA
  3. 3.Jess and Mildred Fisher Center for Hereditary Cancer and Clinical Genomics ResearchGeorgetown Lombardi Comprehensive Cancer CenterWashingtonUSA
  4. 4.Department of OncologyGeorgetown University Medical CenterWashingtonUSA

Personalised recommendations