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  • Poster Presentation
  • Open Access

Independent prognostic value of somatic TP53gene mutations in 1794 breast cancer patients

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Breast Cancer Research20057 (Suppl 2) :P4.48

https://doi.org/10.1186/bcr1178

  • Published:

Keywords

  • Breast Cancer
  • Missense Mutation
  • Node Status
  • Primary Breast Cancer
  • TP53 Mutation

Background

The prognostic significance of TP53 mutations in breast cancer has been investigated in several studies, but the independency of TP53 towards other prognostic factors and the nature of the mutations that may carry a worse prognosis are still unclear.

Methods

Retrospective series of breast cancer cases from 10 hospitals in seven different European countries were combined to assemble a large dataset of clinical and molecular data on 1794 European women with primary breast cancer who were followed-up for 10 years, and whose tumor had been screened for TP53 mutation by gene sequencing. The association between TP53 gene mutation and breast-specific cancer death was examined in univariate and multivariate models including classical prognostic factors of survival.

Results

TP53 gene mutations were more frequent in tumors of ductal and medullar types, aggressive phenotype (high grade, large size, node-positive cases and low hormone receptor contents) and in women under 60 years old. An elevated risk of breast-specific cancer death within 10 years of follow-up was found in patients with a TP53 mutation within exons 5–8 in their tumor compared with patients with no such mutation (relative risk, 2.27; P < 0.0001). This association remained valid after adjustment for tumor size, nodes status and hormone receptor contents. An interaction between TP53 gene mutation and PR content was found, patients with TP53 mutation and negative PR status having a very bad prognosis independently of tumor size, node status and ER status. More importantly, in patients with PR-positive status, TP53 mutation was associated with a strong reduction in survival over 10 years. Among specific types of TP53 mutations, non-missense mutations and missense mutations in the DNA-binding surface (L2/L3 and LSH motifs) had a worse prognosis than mutations outside the DNA-binding surface. Among missense mutations, those at codon 179 and the R248W mutant were associated with the highest mortality rates.

Conclusion

These results clearly show that TP53 gene mutation is an independent factor of prognosis in breast cancer, and advocate its use in clinical practice to improve cancer management.

Declarations

Acknowledgement

This research was supported by EC FP6 funding. This publication reflects the authors' views and not necessarily those of the EC. The EC is not liable for any use that may be made of the information contained herein.

Authors’ Affiliations

(1)
International Agency for Research on Cancer (CIRC/IARC), Lyon, France
(2)
Department of Genetics, The Norwegian Radium Hospital, and University of Oslo, Faculty Division, The Norwegian Radium Hospital, Oslo, Norway
(3)
INSERM U379, ORS PACA, Epidémiologie sociale appliquée à l'innovation, Marseille, France
(4)
Department of Oncology (Radiumhemmet), Karolinska Hospital and Institute, Stockholm, Sweden
(5)
The Icelandic Cancer Society Molecular and Cell Biology Research Laboratory and Faculty of Medicine, University of Iceland, Reykjavik, Iceland
(6)
INSERM E 229, CRLC Val d'Aurelle/Paul Lamarque, Montpellier, France
(7)
INSERM U735/Oncogénétique, Centre René Huguenin, Saint-Cloud, France
(8)
Paterson Institute for Cancer Research, Manchester, UK
(9)
Department of Oncogenetics, Centre Jean Perrin, Clermont-Ferrand, France
(10)
Department of Clinical Genetics, Oulu University Hospital/University of Oulu, Finland
(11)
Department of Oncology, Oulu University Hospital/University of Oulu, Finland
(12)
Molekulargenetisches Labor, Frauenklinik des Universitätsklinikums Düsseldorf, Germany
(13)
Department of Clinical Oncology, Institute of Development Aging and Cancer, Sendai, Japan

Copyright

© BioMed Central 2005

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