Familial Cancer

, Volume 18, Issue 1, pp 127–135 | Cite as

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

  • Fred H MenkoEmail author
  • Jacqueline A ter Stege
  • Lizet E van der Kolk
  • Kiki N Jeanson
  • Winnie Schats
  • Daoud Ait Moha
  • Eveline M A Bleiker


Following the identification in a proband of a germline BRCA1/BRCA2 mutation in hereditary breast-ovarian cancer (HBOC) or a DNA mismatch repair gene mutation in Lynch syndrome (LS) he or she will be asked to inform at-risk family members about the option for presymptomatic DNA testing. However, in clinical practice multiple factors may complicate the process of information sharing. We critically evaluated studies on the uptake of presymptomatic genetic testing in both syndromes. A search of relevant MeSH terms and key words in PubMed, Embase and PsycINFO yielded 795 articles published between 2001 and 2017. Thirty of these publications included outcome measures relevant for the current study. Based on information provided by the proband (15 studies) the uptake of presymptomatic genetic testing ranged from 15 to 57% in HBOC, while one study in LS kindreds reported an uptake of 70%. Based on information provided by genetics centres (the remaining 15 studies) the uptake ranged from 21 to 44% in HBOC and from 41 to 94% in LS. However, when genetics centres contacted relatives directly a substantial number of additional family members could be tested. Proband-mediated provision of information to at-risk relatives is a standard procedure in hereditary breast-ovarian cancer and Lynch syndrome. However, the resulting uptake of presymptomatic testing is disappointing—an issue that is now urgent due to the increased use of genetic testing in clinical oncology. We propose that additional strategies should be introduced including the geneticist directly contacting relatives. The outcomes of these strategies should be carefully monitored and evaluated.


Informing family members Presymptomatic genetic testing Cascade screening Duty to warn Direct contact Hereditary breast-ovarian cancer Lynch syndrome 



Funding was provided by the Dutch Cancer Society (Grant No. NKI 2014-6944).


  1. 1.
    Foulkes WD (2008) Inherited susceptibility to common cancers. N Engl J Med 359:2143–2153CrossRefGoogle Scholar
  2. 2.
    Golmard L, Delnatte C, Laugé A, Moncoutier V, Lefol C, Abidallah K et al (2016) Breast and ovarian cancer predisposition due to de novo BRCA1 and BRCA2 mutations. Oncogene 35:1324–1327CrossRefGoogle Scholar
  3. 3.
    Win AK, Jenkins MA, Buchanan DD, Clendenning M, Young JP, Giles GG et al (2011) Determining the frequency of de novo germline mutations in DNA mismatch repair genes. J Med Genet 48:530–534CrossRefGoogle Scholar
  4. 4.
    Godard B, Hurlimann T, Letendre M, Égalité N, INHERIT BRCAs (2006) Guidelines for disclosing genetic information to family members: from development to use. Fam Cancer 5:103–116CrossRefGoogle Scholar
  5. 5.
    Forrest LE, Delatycki MB, Skene L, Aitken M (2007) Communicating genetic information in families—a review of guidelines and position papers. Eur J Hum Genet 15:612–618CrossRefGoogle Scholar
  6. 6.
    Dheensa S, Fenwick A, Shkedi-Rafid S, Crawford G, Lucassen A (2016) Health-care professionals’ responsibility to patients’ relatives in genetic medicine: a systematic review and synthesis of empirical research. Genet Med 18:290–301CrossRefGoogle Scholar
  7. 7.
    Derbez B, de Pauw A, Stoppa-Lyonnet D, de Montgolfier S (2017) Supporting disclosure of genetic information to family members: professional practice and timelines in cancer genetics. Fam Cancer 16:447–457CrossRefGoogle Scholar
  8. 8.
    Menko FH, Aalfs CM, Henneman L, Stol Y, Wijdenes M, Otten E et al (2013) Informing family members of individuals with Lynch syndrome: a guideline for clinical geneticists. Fam Cancer 12:319–324CrossRefGoogle Scholar
  9. 9.
    Lucassen A, Gilbar R (2018) Alerting relatives about heritable risks: the limits of confidentiality. BMJ. Google Scholar
  10. 10.
    Hughes C, Lerman C, Schwartz M, Peshkin BN, Wenzel L, Narod S et al (2002) All in the family: evaluation of the process and content of sisters’ communication about BRCA1 and BRCA2 genetic test results. Am J Med Genet 107:143–150CrossRefGoogle Scholar
  11. 11.
    Blandy C, Chabal F, Stoppa-Lyonnet D, Julian-Reynier C (2003) Testing participation in BRCA1/2-positive families: initiator role of index cases. Genet Test 7:225–233CrossRefGoogle Scholar
  12. 12.
    Claes E, Evers-Kiebooms G, Boogaerts A, Decruyenaere M, Denayer L, Legius E (2003) Communication with close and distant relatives in the context of genetic testing for hereditary breast and ovarian cancer in cancer patients. Am J Med Genet 116A:11–19CrossRefGoogle Scholar
  13. 13.
    McGivern B, Everett J, Yager GG, Baumiller RC, Hafertepen A, Saal HM (2004) Family communication about positive BRCA1 and BRCA2 genetic test results. Genet Med 6:503–509CrossRefGoogle Scholar
  14. 14.
    Wagner Costalas J, Itzen M, Malick J, Babb JS, Bove B, Godwin AK et al (2003) Communication of BRCA1 and BRCA2 results to at-risk relatives: a cancer risk assessment program’s experience. Am J Med Genet 119C:11–18CrossRefGoogle Scholar
  15. 15.
    Sermijn E, Goelen G, Teugels E, Kaufman L, Bonduelle M, Neyns B et al (2004) The impact of proband mediated information dissemination in families with a BRCA1/2 gene mutation. J Med Genet 41:e23CrossRefGoogle Scholar
  16. 16.
    Landsbergen K, Verhaak C, Kraaimaat F, Hoogerbrugge N (2005) Genetic uptake in BRCA-mutation families is related to emotional and behavioral communication characteristics of index patients. Fam Cancer 4:115–119CrossRefGoogle Scholar
  17. 17.
    Patenaude AF, Dorval M, DiGianni LS, Schneider KA, Chittenden A, Garber JE (2006) Sharing BRCA1/2 test results with first-degree relatives: factors predicting who women tell. J Clin Oncol 24:700–706CrossRefGoogle Scholar
  18. 18.
    Finlay E, Stopfer JE, Burlingame E, Goldfeder Evans K, Nathanson KL, Weber BL et al (2008) Factors determining dissemination of results and uptake of genetic testing in families with known BRCA1/2 mutations. Genet Test 12:81–91CrossRefGoogle Scholar
  19. 19.
    Cheung EL, Olson AD, Yu TM, Han PZ, Beattie MS (2010) Communication of BRCA results and family testing in 1,103 high-risk women. Cancer Epidemiol Biomarkers Prev 19:2211–2219CrossRefGoogle Scholar
  20. 20.
    Fehniger J, Lin F, Beattie MS, Joseph G, Kaplan C (2013) Family communication of BRCA1/2 results and family uptake of BRCA1/2 testing in a diverse population of BRCA1/2 carriers. J Genet Couns 22:603–612CrossRefGoogle Scholar
  21. 21.
    Kegelaers D, Merckx W, Odeurs P, van den Ende J, Blaumeiser B (2014) Disclosure pattern and follow-up after the molecular diagnosis of BRCA/CHEK2 mutations. J Genet Couns 23:254–261CrossRefGoogle Scholar
  22. 22.
    Healey E, Taylor N, Greening S, Wakefield CE, Warwick L, Williams R et al (2017) Quantifying family dissemination and identifying barriers to communication of risk information in Australian BRCA families. Genet Med 19:1323–1331CrossRefGoogle Scholar
  23. 23.
    Stoffel EM, Ford B, Mercado RC, Punglia D, Kohlmann W, Conrad P et al (2008) Sharing genetic test results in Lynch syndrome: communication with close and distant relatives. Clin Gastroenterol Hepatol 6:333–338CrossRefGoogle Scholar
  24. 24.
    Aktan-Collan KI, Kääriäinen HA, Kolttola EM, Pylvänäinen K, Järvinen HJ, Haukkala AH et al (2011) Sharing genetic risk with next generation: mutation-positive parents’ communication with their offspring in Lynch Syndrome. Fam Cancer 10:43–50CrossRefGoogle Scholar
  25. 25.
    Bodd TL, Reichelt J, Heimdal K, Møller P (2003) Uptake of BRCA1 genetic testing in adult sisters and daughters of known mutation carriers in Norway. J Genet Couns 12:405–417CrossRefGoogle Scholar
  26. 26.
    Brooks L, Lennard F, Shenton A, Lalloo F, Ambus I, Ardern-Jones A et al (2004) BRCA1/2 predictive testing: a study of uptake in two centres. Eur J Hum Genet 12:654–662CrossRefGoogle Scholar
  27. 27.
    Suthers GK, Armstrong J, McCormack J, Trott D (2006) Letting the family know: balancing ethics and effectiveness when notifying relatives about genetic testing for a familial disorder. J Med Genet 43:665–670CrossRefGoogle Scholar
  28. 28.
    Cody N, Green A, McDevitt T, Lynch SA (2008) Cascade screening in BRCA1/2 mutation carriers. Ir Med J 101:140–142Google Scholar
  29. 29.
    Holloway SM, Bernhard B, Campbell H, Lam WW (2008) Uptake of testing for BRCA1/2 mutations in South East Scotland. Eur J Hum Genet 16:906–912CrossRefGoogle Scholar
  30. 30.
    Evans DGR, Binchy A, Shenton A, Hopwood P, Craufurd D (2009) Comparison of proactive and usual approaches to offering predictive testing for BRCA1/2 mutations in unaffected relatives. Clin Genet 75:124–132CrossRefGoogle Scholar
  31. 31.
    Sanz J, Ramón y Cajal T, Torres A, Darder E, Gadea N, Velasco A et al (2010) Uptake of predictive testing among relatives of BRCA1 and BRCA2 families: a multicenter study in northeastern Spain. Fam Cancer 9:297–304CrossRefGoogle Scholar
  32. 32.
    Yoon S-Y, Thong M-K, Taib NAM, Yip C-H, Teo S-H (2011) Genetic counseling for patients and families with hereditary breast and ovarian cancer in a developing Asian country: an observational descriptive study. Fam Cancer 10:199–205CrossRefGoogle Scholar
  33. 33.
    Fischer C, Engel C, Sutter C, Zachariae S, Schmutzler R, Meindl A et al (2012) BRCA1/2 testing: uptake, phenocopies, and strategies to improve detection rates in initially negative families. Clin Genet 82:478–483CrossRefGoogle Scholar
  34. 34.
    Sermijn E, Delesie L, Deschepper E, Pauwels I, Bonduelle M, Teugels E et al (2016) The impact of an interventional counselling procedure in families with a BRCA1/2 gene mutation: efficacy and safety. Fam Cancer 15:155–162CrossRefGoogle Scholar
  35. 35.
    Aktan-Collan K, Haukkala A, Pylvänäinen K, Järvinen HJ, Aaltonen LA, Peltomäki P et al (2007) Direct contact in inviting high-risk members of hereditary colon cancer families to genetic counselling and DNA testing. J Med Genet 44:732–738CrossRefGoogle Scholar
  36. 36.
    Ramsoekh D, van Leerdam ME, Tops CMJ, Dooijes D, Steyerberg EW, Kuipers EJ et al (2007) The use of genetic testing in hereditary colorectal cancer syndromes: genetic testing in HNPCC, (A)FAP and MAP. Clin Genet 72:562–567CrossRefGoogle Scholar
  37. 37.
    Bruwer Z, Futter M, Ramesar R (2013) Communicating cancer risk within an African context: experiences, disclosure patterns and uptake rates following genetic testing for Lynch syndrome. Patient Educ Couns 92:53–60CrossRefGoogle Scholar
  38. 38.
    Barrow P, Green K, Clancy T, Lalloo F, Hill J, Evans DG (2015) Improving the uptake of predictive testing and colorectal screening in Lynch syndrome: a regional primary care study. Clin Genet 87:517–524CrossRefGoogle Scholar
  39. 39.
    Seppälä TT, Pylvänäinen K, Mecklin J-P (2017) Uptake of genetic testing by the children of Lynch syndrome variant carriers across three generations. Eur J Hum Genet 25:1237–1245CrossRefGoogle Scholar
  40. 40.
    Daly MB, Montgomery S, Bingler R, Ruth K (2016) Communicating genetic test results within the family: is it lost in translation? A survey of relatives in the randomized six-step study. Fam Cancer 15:697–706CrossRefGoogle Scholar
  41. 41.
    Leenen CHM, den Heijer M, van der Meer C, Kuipers EJ, van Leerdam ME, Wagner A (2016) Genetic testing for Lynch syndrome: family communication and motivation. Fam Cancer 15:63–73CrossRefGoogle Scholar
  42. 42.
    Schneider KA, Chittenden AB, Branda KJ, Keenan MA, Joffe S, Patenaude AF et al (2006) Ethical issues in cancer genetics: 1) Whose information is it? J Genet Couns 15:491–503CrossRefGoogle Scholar
  43. 43.
    Lacroix M, Nycum G, Godard B, Knoppers BM (2008) Should physicians warn patients’ relatives of genetic risks? CMAJ 178:593–595CrossRefGoogle Scholar
  44. 44.
    Black L, McClellan KA, Avard D, Knoppers BM (2013) Intrafamilial disclosure of risk for hereditary breast and ovarian cancer: points to consider. J Community Genet 4:203–214CrossRefGoogle Scholar
  45. 45.
    George R, Kovak K, Cox SL (2015) Aligning policy to promote cascade genetic screening for prevention and early diagnosis of heritable diseases. J Genet Couns 24:388–399CrossRefGoogle Scholar
  46. 46.
    Weaver M (2016) The double helix: applying an ethic of care to the duty to warn genetic relatives of genetic information. Bioethics 30:181–187CrossRefGoogle Scholar
  47. 47.
    Mitchell C, Ploem MC, Chico V, Ormondroyd E, Hall A, Wallace S et al (2017) Exploring the potential duty of care in clinical genomics under UK Law. Med Law Int 17:158–182CrossRefGoogle Scholar
  48. 48.
    Dheensa S, Fenwick A, Lucassen A (2016) “Is this knowledge mine and nobody else’s? I don’t feel that.” Patient views about consent, confidentiality and information-sharing in genetic medicine. J Med Ethics 42:174–179CrossRefGoogle Scholar
  49. 49.
    Committee on Genetics, American College of Obstetricians and Gynecologists (2017) Counseling about genetic testing and communication of genetic test results. Obstet Gynecol 129: e96-e101Google Scholar
  50. 50.
    D’Audiffret Van Haecke D, de Montgolfier S (2018) Genetic diseases and information to relatives: practical and ethical issues for professionals after introduction of a legal framework in France. Eur J Hum Genet. Google Scholar
  51. 51.
    Rothstein MA (2018) Reconsidering the duty to warn genetically at-risk relatives. Genet Med 20:285–290CrossRefGoogle Scholar
  52. 52.
    Parker M, Lucassen A (2018) Using a genetic test result in the care of family members: how does the duty of confidentiality apply? Eur J Hum Genet. Google Scholar
  53. 53.
    Montgomery SV, Barsevick AM, Egleston BL, Bingler R, Ruth K, Miller SM et al (2013) Preparing individuals to communicate genetic test results to their relatives: report of a randomized control trial. Fam Cancer 12:537–546CrossRefGoogle Scholar
  54. 54.
    Geus de E, Aalfs CM, Verdam MGE, de Haes HCJM, Smets EMA (2014) Informing relatives about their hereditary or familial cancer risk: study protocol for a randomized controlled trial. Trials 15:86CrossRefGoogle Scholar
  55. 55.
    Hodgson J, Metcalfe S, Gaff C, Donath S, Delatycki MB, Winship I et al (2016) Outcomes of a randomised controlled trial of a complex genetic counselling intervention to improve family communication. Eur J Hum Genet 24:356–360CrossRefGoogle Scholar
  56. 56.
    Ratnayake P, Wakefield CE, Meiser B, Suthers G, Price MA, Duffy J et al (2011) An exploration of the communication preferences regarding genetic testing in individuals from families with identified breast/ovarian cancer mutations. Fam Cancer 10:97–105CrossRefGoogle Scholar
  57. 57.
    Kardashian A, Fehniger J, Creasman J, Cheung E, Beattie MS (2012) A pilot study of the sharing risk information tool (ShaRIT) for families with hereditary breast and ovarian cancer syndrome. Hered Cancer Clin Pract 10:4CrossRefGoogle Scholar
  58. 58.
    Dilzell K, Kingham K, Ormond K, Ladabaum U (2014) Evaluating the utilization of educational materials in communicating about Lynch syndrome to at-risk relatives. Fam Cancer 13:381–389CrossRefGoogle Scholar
  59. 59.
    Dheensa S, Lucassen A, Fenwick A (2018) Limitations and pitfalls of using family letters to communicate genetic risk: a qualitative study with patients and healthcare professionals. J Genet Couns 27:689–701CrossRefGoogle Scholar
  60. 60.
    Forrest LE, Burke J, Bacic S, Amor DJ (2008) Increased genetic counseling support improves communication of information in families. Genet Med 10:167–172CrossRefGoogle Scholar
  61. 61.
    Jasperson K (2013) Cascade genetic testing in Lynch syndrome: room for improvement. Nat Rev Gastroenterol Hepatol 10:506–508CrossRefGoogle Scholar
  62. 62.
    Hampel H (2016) Genetic counseling and cascade genetic testing in Lynch syndrome. Fam Cancer 15:423–427CrossRefGoogle Scholar
  63. 63.
    Mendes A, Paneque M, Sousa L, Clarke A, Sequeiros J et al (2016) How communication of genetic information within the family is addressed in genetic counselling: a systematic review of research evidence. Eur J Hum Genet 24:315–325CrossRefGoogle Scholar
  64. 64.
    Katapodi MC, Viassolo V, Caiata-Zufferey M, Nikolaidis C, Bührer-Landolt R, Buerki N et al (2017) Cancer predisposition cascade screening for hereditary breast/ovarian cancer and Lynch syndromes in Switzerland: study protocol. JMIR Res Protoc 6:e184CrossRefGoogle Scholar
  65. 65.
    Tung N, Domchek SM, Stadler Z, Nathanson KL, Couch F, Garber JE et al (2016) Counselling framework for moderate-penetrance cancer-susceptibility mutations. Nat Rev Clin Oncol 13:581–588CrossRefGoogle Scholar
  66. 66.
    Vos J, Jansen AM, Menko F, van Asperen CJ, Stiggelbout AM, Tibben A (2011) Family communication matters: the impact of telling relatives about unclassified variants and uninformative DNA-test results. Genet Med 13:333–341CrossRefGoogle Scholar
  67. 67.
    Moghadasi S, Hofland N, Wouts JN, Hogervorst FBL, Wijnen JT, Vreeswijk MPG et al (2013) Variants of uncertain significance in BRCA1 and BRCA2 assessment of in silico analysis and a proposal for communication in genetic counselling. J Med Genet 50:74–79CrossRefGoogle Scholar
  68. 68.
    Catenacci DVT, 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 136:1559–1567CrossRefGoogle Scholar
  69. 69.
    Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaňa J et al (2015) Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol 33:244–250CrossRefGoogle Scholar
  70. 70.
    Bednar EM, Oakley HD, Sun CC, Burke CC, Munsell MF, Westin SN et al (2017) A universal genetic testing initiative for patients with high-grade, non-mucinous epithelial ovarian cancer and the implications for cancer treatment. Gynecol Oncol 146:399–404CrossRefGoogle Scholar
  71. 71.
    Mandelker D, Zhang L, Kemel Y, Stadler ZK, Joseph V, Zehir A et al (2017) 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 318:825–835CrossRefGoogle Scholar
  72. 72.
    Narod S, Akbari MR (2018) Population-based genetic testing for BRCA1 and BRCA2. J Clin Oncol 36:517CrossRefGoogle Scholar
  73. 73.
    Forrest LE, Young M-A (2016) Clinically significant germline mutations in cancer-causing genes identified through research studies should be offered to research participants by genetic counselors. J Clin Oncol 34:898–901CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Fred H Menko
    • 1
    Email author
  • Jacqueline A ter Stege
    • 2
  • Lizet E van der Kolk
    • 1
  • Kiki N Jeanson
    • 1
  • Winnie Schats
    • 3
  • Daoud Ait Moha
    • 1
  • Eveline M A Bleiker
    • 2
  1. 1.Family Cancer ClinicAntoni van Leeuwenhoek Hospital and The Netherlands Cancer InstituteAmsterdamThe Netherlands
  2. 2.Department of Psychosocial Research and EpidemiologyAntoni van Leeuwenhoek Hospital and The Netherlands Cancer InstituteAmsterdamThe Netherlands
  3. 3.Department of Scientific Information ServiceAntoni van Leeuwenhoek Hospital and The Netherlands Cancer InstituteAmsterdamThe Netherlands

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