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

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Summary

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.

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Authors and Affiliations

  1. Division of Medical Oncology, University of Texas Health Science Center, 7703 Floyd Curl Drive, 78284-7884, San Antonio, Texas, USA

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

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  1. Richard M. Elledge
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  2. Suzanne A. W. Fuqua
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  3. Gary M. Clark
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  4. Pascal Pujol
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  5. D. Craig Allred
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  6. William L. McGuire
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Additional information

We regret to report that Dr. McGuire died March 25, 1992, while this work was in progress.

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Elledge, R.M., Fuqua, S.A.W., Clark, G.M. et al. Prognostic significance of p53 gene alterations in node-negative breast cancer. Breast Cancer Res Tr 26, 225–235 (1993). https://doi.org/10.1007/BF00665800

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