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Independent prognostic value of somatic TP53gene mutations in 1794 breast cancer patients
Breast Cancer Research volume 7, Article number: P4.48 (2005)
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.
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.
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.
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.
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.
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Olivier, M., Langerød, A., Carrieri, P. et al. Independent prognostic value of somatic TP53gene mutations in 1794 breast cancer patients. Breast Cancer Res 7, P4.48 (2005). https://doi.org/10.1186/bcr1178
- Breast Cancer
- Missense Mutation
- Node Status
- Primary Breast Cancer
- TP53 Mutation