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Impact of germline BRCA1 mutations and overexpression of p53 on prognosis and response to treatment following breast carcinoma
10-Year follow-up data
Article first published online: 17 JAN 2003
Copyright © 2003 American Cancer Society
Volume 97, Issue 3, pages 527–536, 1 February 2003
How to Cite
Goffin, J. R., Chappuis, P. O., Bégin, L. R., Wong, N., Brunet, J.-S., Hamel, N., Paradis, A.-J., Boyd, J. and Foulkes, W. D. (2003), Impact of germline BRCA1 mutations and overexpression of p53 on prognosis and response to treatment following breast carcinoma. Cancer, 97: 527–536. doi: 10.1002/cncr.11080
- Issue published online: 17 JAN 2003
- Article first published online: 17 JAN 2003
- Manuscript Accepted: 5 SEP 2002
- Manuscript Revised: 19 AUG 2002
- Manuscript Received: 21 JUN 2002
- U.S. Army. Grant Number: DAMD17-98-1-8112
- Canadian Genetic Diseases Network
- Fonds de la Recherche en Santé du Québec (FRSQ-Réseau Cancer: Axe Cancer du sein et de l'ovaire)
- la Ligue Genevoise contre le Cancer and Cancer & Solidarité Fondation, Geneva, Switzerland
- National Cancer Institute of Canada Clinical Trials Group
- breast neoplasms;
- protein p53;
- adjuvant chemotherapy;
- neoplastic syndromes;
Overexpression of p53 has been associated with poor survival following breast carcinoma. BRCA1 interacts biochemically with p53 and may also contribute to poor outcome when constitutionally mutated. The joint effect of both abnormalities has not been studied. The primary objective of this study was to assess the impact of germline BRCA1 mutations and p53 overexpression on survival after 10 years of follow-up.
A historical cohort of Ashkenazi Jewish women 65 years or younger with invasive breast carcinoma was tested for BRCA1 founder mutations. p53 overexpression was assessed by immunohistochemistry. Clinicopathologic information was obtained by chart review.
In total, 278 women were analyzed. On univariate analysis, p53 overexpression (n = 63) was prognostic for worse overall survival (relative risk [RR] 2.6, P = 0.001) whereas BRCA1 germline mutations (n = 30) were of borderline significance (RR 1.9, P = 0.052). In the lymph node-negative subpopulation, BRCA1 mutation status conferred a higher mortality on univariate (RR 5.6, P < 0.001) and multivariate (RR 3.5, P = 0.03) analyses. There was a trend in favor of a worse prognosis for women who carried a germline BRCA1 mutation and whose tumor overexpressed p53. When compared with noncarriers, BRCA1 mutation carriers had a worse overall survival if they did not receive adjuvant chemotherapy (RR 3.3, P= 0.01) or adjuvant hormonal therapy (RR 2.3, P = 0.02).
Germline BRCA1 mutations and p53 overexpression carry a negative prognosis that is not additive to known prognostic factors. Given the experimental sensitivity of BRCA1-mutated cells to chemotherapy, the worse survival among BRCA1 mutation-carrying lymph node-negative breast carcinoma patients may be partly explained by the significantly lower proportion of lymph node-negative patients who received adjuvant chemotherapy (P < 0.001). Cancer 2003;97:527–36. © 2003 American Cancer Society.