Prognostic significance of p53 gene alterations in node-negative breast cancer

Richard M. Elledge, Suzanne A.W. Fuqua, Gary M. Clark, Pascal Pujol, D. Craig Allred, William L. McGuire

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Mutations in the p53 gene can play a role in the transformation of normal to malignant cells. Because these mutations are more frequently reported later in the course of transformation, their presence could reflect a greater malignant potential of the tumor and, thus, an increased probability of metastasis and recurrence after local therapy. In a pilot study using single-stranded conformation polymorphism analysis (SSCP), 200 node-negative breast tumors were examined for mutations in the region encompassing exons 5 through 9 of the p53 gene. Exons 5 through 9 were tested because they contain 80-90% of known p53 gene mutations. The tumors ranged in size from 1 to 3 cm. 28 tumors were found to have an abnormal band pattern on both initial and repeat analysis. 4 of these tumors were sequenced; 3 contained a p53 mutation and the 4th had a rare neutral polymorphism. Disease-free survival (DFS) at 5 years for women with tumors having an abnormal SSCP analysis was 57% (± 10%), compared to a 79% (± 3%) DFS for the group with a normal pattern. By the log rank test, this difference was highly significant, p ≤ 0.01. The relative risk of recurrence for the group with an abnormal SSCP pattern was 2.2. In a multivariate analysis including ER, PgR, ploidy, S-phase, age, and tumor size, an abnormal p53 by SSCP analysis and patient age were the only factors that independently predicted DFS at 5 years. Conclusion: Women with node-negative breast cancer who have tumors with alterations in the p53 gene, as indicated by SSCP analysis, have a significantly poorer prognosis and a higher rate of relapse at 5 years. The prognostic significance is maintained in a multivariate analysis including many established prognostic factors.

Original languageEnglish (US)
Pages (from-to)225-235
Number of pages11
JournalBreast Cancer Research and Treatment
Volume26
Issue number3
DOIs
StatePublished - Jan 1993

Keywords

  • breast cancer
  • p53 gene
  • p53 protein
  • prognostic factor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Elledge, R. M., Fuqua, S. A. W., Clark, G. M., Pujol, P., Allred, D. C., & McGuire, W. L. (1993). Prognostic significance of p53 gene alterations in node-negative breast cancer. Breast Cancer Research and Treatment, 26(3), 225-235. https://doi.org/10.1007/BF00665800