A novel HER2-positive breast cancer phenotype arising from germline TP53 mutations

Jamie R F Wilson (1) , Adrian C Bateman (2) , Helen Hanson (3) , Qian An (4) , Gareth D. Evans (5) , Nazneen Rahman (3) , Louise J Jones (6) , Diana M Eccles (4)

1 Wessex Clinical Genetics Service, Southampton University Hospitals Trust
2 Department of Cellular Pathology, Southampton University Hospitals Trust
3 Institute of Cancer Research, Belmont, Sutton
4 University of Southampton
5 Genetic Medicine, Manchester Academic Health Centre, Central Manchester Foundation Trust
6 Centre for Tumour Biology, Institute of Cancer, Barts and the London School of Medicine

INTRODUCTION: The Li-Fraumeni Syndrome (LFS) 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 recognized 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 9 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.

Mots clés: Diagnosis; Lipid disorders; Clinical genetics; Oncology; Cancer: breast

Jamie R F Wilson, Adrian C Bateman, Helen Hanson, Qian An, Gareth D. Evans, et al.. A novel HER2-positive breast cancer phenotype arising from germline TP53 mutations. Journal of Medical Genetics, 2010, 47 (11), pp.771. ⟨10.1136/jmg.2010.078113⟩. ⟨hal-00560779⟩