Advertisement

Familial Cancer

, Volume 16, Issue 3, pp 423–432 | Cite as

Psychosocial morbidity in TP53 mutation carriers: is whole-body cancer screening beneficial?

  • Kate A. McBrideEmail author
  • Mandy L. Ballinger
  • Timothy E. Schlub
  • Mary-Anne Young
  • Martin H. N. Tattersall
  • Judy Kirk
  • Ros Eeles
  • Emma Killick
  • Leslie G. Walker
  • Sue Shanley
  • David M. Thomas
  • Gillian Mitchell
Original Article

Abstract

Germline TP53 mutation carriers are at high risk of developing a range of cancers. Effective cancer risk management is an important issue for these individuals. We assessed the psychosocial impact in TP53 mutation carriers of WB-MRI screening as part of the Surveillance in Multi-Organ Cancer (SMOC+) protocol, measuring their unmet needs, anxiety and depression levels as well as cancer worry using psychological questionnaires and in-depth interviews about their experiences of screening. We present preliminary psychosocial findings from 17 participants during their first 12 months on the trial. We found a significant reduction in participants’ mean anxiety from baseline to two weeks post WB-MRI (1.2, 95% CI 0.17 to 2.23 p = 0.025), indicative of some benefit. Emerging qualitative themes show most participants are emotionally supported and contained by the screening program and are motivated by their immediate concern about staying alive, despite being informed about the current lack of evidence around efficacy of screening for people with TP53 mutations in terms of cancer morbidity or mortality. For those that do gain emotional reassurance from participating in the screening study, feelings of abandonment by the research team are a risk when the study ends. For others, screening was seen as a burden, consistent with the relentless nature of cancer risk associated with Li-Fraumeni syndrome, though these patients still declared they wished to participate due to their concern with staying alive. Families with TP53 mutations need ongoing support due to the impact on the whole family system. These findings suggest a comprehensive multi-organ screening program for people with TP53 mutations provides psychological benefit independent of an impact on cancer morbidity and mortality associated with the syndrome. The benefits of a multi-organ screening program will be greater still if the screening tests additionally reduce the cancer morbidity and mortality associated with the syndrome. These findings may also inform the care of individuals and families with other multi-organ cancer predisposition syndromes.

Keywords

Li-Fraumeni syndrome TP53 Screening Hereditary cancer Psychosocial Mixed methods 

Supplementary material

10689_2016_9964_MOESM1_ESM.doc (812 kb)
Supplementary material 1 (DOC 811 KB)

References

  1. 1.
    Malkin D (2011) Li-fraumeni syndrome. Genes cancer 2(4):475–484CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Kamihara J, Rana HQ, Garber JE (2014) Germline TP53 Mutations and the Changing Landscape of Li-Fraumeni Syndrome. Hum Mutat 35(6):654–662. doi: 10.1002/humu.22559 CrossRefPubMedGoogle Scholar
  3. 3.
    McBride KA, Ballinger ML, Killick E et al (2014) Li-Fraumeni syndrome: cancer risk assessment and clinical management. Nature Reviews. Clin Oncol 11(5):260–271. doi: 10.1038/nrclinonc.2014.41 Google Scholar
  4. 4.
    Li FP, Fraumeni JF, Mulvihill JJ, et al. (1988) A cancer family syndrome in 24 kindreds. Cancer Research 48(18): 5358–5362Google Scholar
  5. 5.
    Ruijs MWG, Verhoef S, Rookus MA et al (2010) TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J Med Genet 47(6):421–428. doi: 10.1136/jmg.2009.073429 CrossRefPubMedGoogle Scholar
  6. 6.
    Bougeard G, Renaux-Petel M, Flama J-M, et al. (2015) Revisiting Li-Fraumeni Syndrome from TP53 mutation carriers. Journal of Clinical Oncology Published ahead of print: doi:  10.1200/JCO.2014.59.5728 Google Scholar
  7. 7.
    Hwang SJ, Lozano G, Amos CI, Strong LC (2003) Germline p53 mutations in a cohort with childhood sarcoma: Sex differences in cancer risk. Am J Hum Genet 72(4):975–983CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lustbader ED, Williams WR, Bondy ML, Strom S, Strong LC (1992) Segregation analysis of cancer in families of childhood soft-tissue-sarcoma patients. Am J Hum Genet 51(2):344–356PubMedPubMedCentralGoogle Scholar
  9. 9.
    Limacher JM, Frebourg T, Natarajan-Ame S, Bergerat JP (2001) Two metachronous tumors in the radiotherapy fields of a patient with Li-Fraumeni syndrome. Int J Cancer 96(4):238–242. doi: 10.1002/ijc.1021 CrossRefPubMedGoogle Scholar
  10. 10.
    Chadaz T, Hobbs SK, Son H (2013) Chest Wall Sarcoma F-18-FDG PET/CT in a Patient With Li-Fraumeni Syndrome. Clin Nucl Med 38(10):818–820CrossRefPubMedGoogle Scholar
  11. 11.
    Peters J, Kene R, Bremer R, Givens S, Savage S, Mai P (2015) Easing the Burden: Describing the Role of Social, Emotional and Spiritual Support in Research Families with Li-Fraumeni Syndrome. Journal of Genetic CounselingGoogle Scholar
  12. 12.
    Evans DG, Lunt P, Clancy T, Eeles R (2010) Childhood predictive genetic testing for Li-Fraumeni syndrome. Familial Cancer 9(1):65–69. doi: 10.1007/s10689-009-9245-9 CrossRefPubMedGoogle Scholar
  13. 13.
    Australia New Zealand Clinical Trials Registry (2013 September 4) A pilot surveillance study investigating whole body magnetic resonance imaging and other diagnostic procedures in people at high risk of cancer (SMOC) ACTRN12613000987763. http://www.ANZCTR.org.au/ACTRN12613000987763.aspx. Sydney (NSW), NHMRC Clinical Trials Centre, University of Sydney (Australia)
  14. 14.
    ClinicalTrials.gov (2011 October 31) LIFSCREEN : Evaluation of Whole Body MRI for Early Detection of Cancers in Subjects With P53 Mutation (Li-Fraumeni Syndrome) NCT01464086. Bethsheda (MD), National Library of Medicine (US)Google Scholar
  15. 15.
    Clinicaltrials.gov (2012 27 November) Magnetic Resonance Imaging Screening in Li Fraumeni Syndrome (SIGNIFY)NCT01737255. In (US) NLoM (ed). vol. 28 January. Bethsheda (MD)Google Scholar
  16. 16.
    Patenaude AF, Schneider KA, Kieffer SA et al (1996) Acceptance of invitations for p53 and BRCA1 predisposition testing: Factors influencing potential utilization of cancer genetic testing. Psycho-Oncology 5(3):241–250. doi: 10.1002/(sici)1099-1611(199609)5:3 3.3.co;2-yCrossRefGoogle Scholar
  17. 17.
    Lammens CRM, Bleiker EMA, Aaronson NK et al (2010) Regular surveillance for Li-fraumeni syndrome: advice, adherence and perceived benefits. Familial Cancer 9(4):647–654. doi: 10.1007/s10689-010-9368-z CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Maheu C, Vodermaier A, Rothenmund H et al (2010) Pancreatic cancer risk counselling and screening: impact on perceived risk and psychological functioning. Familial Cancer 9(4):617–624. doi: 10.1007/s10689-010-9354-5 CrossRefPubMedGoogle Scholar
  19. 19.
    Hutton J, Walker LG, Gilbert FJ et al (2011) Psychological impact and acceptability of magnetic resonance imaging and X-ray mammography: the MARIBS Study. Br J Cancer 104(4):578–586. doi: 10.1038/bjc.2011.1 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Gopie JP, Vasen HFA, Tibben A (2012) Surveillance for hereditary cancer: Does the benefit outweigh the psychological burden?-A systematic review. Critical Reviews in Oncology Hematology 83(3): doi: 10.1016/j.critrevonc.2012.01.004 Google Scholar
  21. 21.
    Teddlie C, Tashakkori A (2009) The foundations of mixed methods research: Integrating quantitative and qualitative techniques in the social and behavioural sciences. Sage, Thousand Oaks, CAGoogle Scholar
  22. 22.
    Tashakkori A, Teddlie C (2010) Sage Handbook of Mixed Methods in Social & Behavioral Research, 2nd edn. Sage, Thousand OaksCrossRefGoogle Scholar
  23. 23.
    Creswell JW (1994) Research design: Qualitative and quantitative approaches. Thousand Oaks, CAGoogle Scholar
  24. 24.
    Patton MQ (2002) Qualitative Research and evaluation methods. Sage, Thousand OaksGoogle Scholar
  25. 25.
    Zigmond AS, Snaith RP (1983) The Hospital Anxiety and depression scale. Acta Psychiatr Scand 67(6):361–370. doi: 10.1111/j.1600-0447.1983.tb09716.x CrossRefPubMedGoogle Scholar
  26. 26.
    Horowitz M, Wilner N, Alvarez W (1979) Impact of event scale—measure of subjective stress. Psychosom Med 41(3):209–218CrossRefPubMedGoogle Scholar
  27. 27.
    Lerman C, Narod S, Schulman K, et al. (1996) BRCA1 testing in families with hereditary breast-ovarian cancer - A prospective study of patient decision making and outcomes. Jama-Journal of the American Medical Association 275(24): 1885–92 doi: 10.1001/jama.275.24.1885
  28. 28.
    Lerman C, Trock B, Rimer BK, Jepson C, Brody D, Boyce A (1991) Psychological side-effects of breast cancer screening. Health Psychol 10(4):259–267. doi: 10.1037/0278-6133.10.4.259 CrossRefPubMedGoogle Scholar
  29. 29.
    Douma KFL, Aaronson NK, Vasen HFA et al (2010) Psychological distress and use of psychosocial support in familial adenomatous polyposis. Psycho-Oncology 19(3):289–298. doi: 10.1002/pon.1570 CrossRefPubMedGoogle Scholar
  30. 30.
    IBM Corp (2012) IBM SPSS Statistics for Windows, Version 21.0, IBM Corp., Armonk, NYGoogle Scholar
  31. 31.
    Custers JAE, van den Berg SW, van Laarhoven HWM, Bleiker EMA, Gielissen MFM, Prins JB (2014) The cancer worry scale detecting fear of recurrence in breast cancer survivors. Cancer Nurs 37(1):E44–E50. doi: 10.1097/NCC.0b013e3182813a17 CrossRefPubMedGoogle Scholar
  32. 32.
    Lammens CRM, Aaronson NK, Wagner A et al (2010) Genetic testing in li-fraumeni syndrome: uptake and psychosocial consequences. J Clin Oncol 28(18):3008–3014. doi: 10.1200/jco.2009.27.2112 CrossRefPubMedGoogle Scholar
  33. 33.
    Peterson SK, Pentz RD, Marani SK et al (2008) Psychological functioning in persons considering genetic counseling and testing for Li-Fraumeni syndrome. Psycho-Oncology 17(8):783–789. doi: 10.1002/pon.1352 CrossRefPubMedGoogle Scholar
  34. 34.
    Dewey M, Schink T, Dewey CF (2007) Claustrophobia during magnetic resonance imaging: Cohort study in over 55,000 patients. J Magn Reson Imaging 26(5):1322–1327. doi: 10.1002/jmri.21147 CrossRefPubMedGoogle Scholar
  35. 35.
    Tazegul G, Etcioglu E, Yildiz F, Yildiz R, Tuney D (2015) Can MRI related patient anxiety be prevented? Magn Reson Imaging 33(1):180–183. doi: 10.1016/j.mri.2014.08.024 CrossRefPubMedGoogle Scholar
  36. 36.
    Caruso A, Bongiorno L, Vallini I, Russo P, Tomao F, Grandinetti ML (2006) Breast cancer and distress resulting from magnetic resonance imaging (MRI): the impact of a psychological intervention of emotional and informative support. J Exp Clin Cancer Res 25(4):499–505PubMedGoogle Scholar
  37. 37.
    Townsend A, Cox SM (2013) Accessing health services through the back door: a qualitative interview study investigating reasons why people participate in health research in Canada. Bmc Med Ethics 14: doi: 10.1186/1472-6939-14-40
  38. 38.
    Power TE, Robinson JW, Bridge P, Bernier FP, Gilchrist DM (2011) Distress and psychosocial needs of a heterogeneous high risk familial cancer population. J Genet Couns 20(3):249–269. doi: 10.1007/s10897-010-9344-7 CrossRefPubMedGoogle Scholar
  39. 39.
    Brennan ME, Robinson K, Brand A, Kirk J (2008) A multidisciplinary risk management clinic for women at high genetic risk of breast and ovarian cancer - Experience and evaluation. Breast 17(2):206–207. doi: 10.1016/j.breast.2007.11.021 CrossRefGoogle Scholar
  40. 40.
    White VM, Young M-A, Farrelly A et al (2014) Randomized Controlled Trial of a Telephone-Based Peer-Support Program for Women Carrying a BRCA1 or BRCA2 Mutation: Impact on Psychological Distress. J Clin Oncol 32(36):4073–4285. doi: 10.1200/jco.2013.54.1607 CrossRefPubMedGoogle Scholar
  41. 41.
    Iredale R, Mundy L, Hilgart J (2011) An online resource of digital stories about cancer genetics: qualitative study of patient preferences and information needs. J Med Internet Res 13(3): doi: 10.2196/jmir.1735 PubMedPubMedCentralGoogle Scholar
  42. 42.
    Landsbergen KM, Brunner HG, Manders P, Hoogerbrugge N, Prins JB (2010) Educational-support groups for BRCA mutation carriers satisfy the need for information but do not affect emotional distress. Genet Couns 21(4):423–437PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  • Kate A. McBride
    • 1
    • 2
    Email author
  • Mandy L. Ballinger
    • 3
  • Timothy E. Schlub
    • 2
  • Mary-Anne Young
    • 4
  • Martin H. N. Tattersall
    • 5
  • Judy Kirk
    • 6
  • Ros Eeles
    • 7
  • Emma Killick
    • 8
  • Leslie G. Walker
    • 9
  • Sue Shanley
    • 4
  • David M. Thomas
    • 3
  • Gillian Mitchell
    • 4
    • 10
  1. 1.School of Science and Health and Centre for Health ResearchWestern Sydney UniversityCampbelltownAustralia
  2. 2.Sydney School of Public HealthCamperdownAustralia
  3. 3.The Kinghorn Cancer CentreGarvan Institute of Medical ResearchDarlinghurstAustralia
  4. 4.Familial Cancer ClinicPeter MacCallum Cancer CentreE. MelbourneAustralia
  5. 5.Department of Cancer Medicine, The Chris O’Brien LifehouseSydney Medical SchoolCamperdownAustralia
  6. 6.The Familial Cancer ServiceCrown Princess Mary Cancer CentreWestmeadAustralia
  7. 7.OncogeneticsThe Institute of Cancer ResearchLondonUK
  8. 8.Medical Oncology UnitUniversity Hospital Southampton NHS Foundation TrustSouthamptonUK
  9. 9.University of HullKingston upon HullUK
  10. 10.Sir Peter MacCallum Dept. of OncologyUniversity of MelbourneParkvilleAustralia

Personalised recommendations