Review Article | Published:

Li-Fraumeni syndrome: cancer risk assessment and clinical management

Nature Reviews Clinical Oncology volume 11, pages 260271 (2014) | Download Citation

Abstract

Carriers of germline mutations in the TP53 gene, encoding the cell-cycle regulator and tumour suppressor p53, have a markedly increased risk of cancer-related morbidity and mortality during both childhood and adulthood, and thus require appropriate and effective cancer risk management. However, the predisposition of such patients to multiorgan tumorigenesis presents a specific challenge for cancer risk management programmes. Herein, we review the clinical implications of germline mutations in TP53 and the evidence for cancer screening and prevention strategies in individuals carrying such mutations, as well as examining the potential psychosocial implications of lifelong management for a ubiquitous cancer risk. In addition, we propose an evidence-based framework for the clinical management of TP53 mutation carriers and provide a platform for addressing the management of other cancer predisposition syndromes that can affect multiple organs.

Key points

  • Inherited cancer predisposition syndromes are increasingly diagnosed due to greater public awareness of germline genetic testing, and also as an incidental finding when somatic mutation testing for 'druggable targets'

  • Some inherited cancer syndromes predispose to cancers at multiple sites, such as Li-Fraumeni syndrome (LFS) caused by germline TP53 mutations, requiring a whole-body approach to cancer risk management

  • The 5-year, 10-year and lifetime cancer risk of many the LFS-associated cancers remains unclear and further study is required to provide such data, which can guide cancer risk management

  • At present, a limited number of validated screening tests for LFS-associated cancers exist, and no validated screening tests have been studied specifically in people with LFS

  • Prospective trials studying the utility and the psychosocial effects of a whole-body approach to screening in LFS are in progress

  • A pragmatic schedule for a whole-body approach to screening is proposed while the results of the prospective trials are awaited

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Author information

Affiliations

  1. The Familial Cancer Service, Crown Princess Mary Cancer Centre, Sydney Medical School, Westmead Millennium Institute, Westmead, NSW 2145, Australia.

    • Kate A. McBride
    •  & Judy Kirk
  2. Research Division, Sir Peter MacCallum Department of Oncology, University of Melbourne, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia.

    • Mandy L. Ballinger
  3. The Familial Cancer Centre, Sir Peter MacCallum Department of Oncology, University of Melbourne, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia.

    • Gillian Mitchell
  4. Medical Oncology Unit, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK.

    • Emma Killick
  5. Department of Cancer Medicine, Sydney Medical School, Royal Prince Alfred Hospital, Camperdown, NSW 2040, Australia.

    • Martin H. N. Tattersall
  6. Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, UK.

    • Rosalind A. Eeles
  7. The Kinghorn Cancer Centre and Garvan Institute, Darlinghurst, NSW 2010, Australia.

    • David M. Thomas

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Contributions

D.M.T. and G.M. contributed equally to this Review. K.A.M. researched the data for the article. All authors contributed substantially to discussion of content, the writing of the article review and/or editing of the manuscript before submission.

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The authors declare no competing financial interests.

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Correspondence to Gillian Mitchell.

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https://doi.org/10.1038/nrclinonc.2014.41

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