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A novel HER2-positive breast cancer phenotype arising from germline TP53 mutations
  1. J R F Wilson1,2,
  2. A C Bateman3,
  3. H Hanson4,
  4. Q An2,5,
  5. G Evans6,
  6. N Rahman4,
  7. J L Jones7,
  8. D M Eccles1,2
  1. 1Wessex Clinical Genetics Service, Southampton University Hospitals Trust, Princess Anne Hospital, Southampton, UK
  2. 2University of Southampton School of Medicine, Cancer Sciences Division, Somers Cancer Research Building, Southampton, UK
  3. 3Department of Cellular Pathology, Southampton University Hospitals Trust, Southampton General Hospital, Southampton, UK
  4. 4Institute of Cancer Research, Belmont, Sutton, Surrey, UK
  5. 5Neuro-oncology Group, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK
  6. 6Centre for Tumour Biology, Institute of Cancer, Barts and the London School of Medicine and Dentistry, London, UK
  7. 7Genetic Medicine, Manchester Academic Health Science Centre, St Mary's Hospital, Central Manchester Foundation Trust, Manchester, UK
  1. Correspondence to Diana Eccles, Wessex Clinical Genetics Service, Southampton University Hospitals Trust, Princess Anne Hospital, Level G, Southampton SO16 5YA, UK; d.m.eccles{at}


Introduction The Li–Fraumeni Syndrome is caused by a germline TP53 mutation and is associated with a high risk of breast cancer at young ages. Basal (triple negative) breast cancers are now well recognised to be a typical sub-type of breast cancer developing in a large proportion of BRCA1 gene carriers. We considered whether a similar narrow sub-type of breast cancer was found in TP53 gene mutation carriers.

Objective A hypothesis generating study to investigate whether there are specific breast tumour characteristics associated with germline TP53 mutations.

Methods Pathological characteristics in 12 breast cancers arising in nine patients carrying pathogenic TP53 mutations were compared to a reference panel of 231 young onset breast tumours included in the POSH study.

Results Patients carrying a TP53 mutation showed a significantly higher likelihood of developing a breast cancer with Human Epidermal growth factor Receptor (HER2) amplification (83%) when compared to the cohort of young onset breast cancer cases (16%); ER and PR status were equivalent between groups.

Conclusion These findings suggest that breast cancer developing on a background of an inherited TP53 mutation is highly likely to present with amplification of HER2.

  • TP53
  • Li–Fraumeni
  • breast cancer
  • pathology
  • early onset
  • diagnosis
  • lipid disorders
  • clinical genetics
  • oncology

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  • Funding 1) Cancer Research UK, P.O. Box 123, Lincoln's Inn Fields, London WC2A 3PX

    2) Breast Cancer Campaign, Clifton Centre, 110 Clifton Street, London EC2A 4HT

    3) Wessex Cancer Trust, Bellis House, 11 Westwood Road, Southampton SO17 1DL.

  • Competing interests None declared.

  • Ethics approval This study was conducted with the approval of the South and West Multi-centre Research Ethics Committee (MREC 00/6/69).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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