Germline BRCA1/2 mutations and p27Kip1 protein levels independently predict outcome after breast cancer

P. O. Chappuis, L. Kapusta, L. R. Bégin, N. Wong, J. S. Brunet, S. A. Narod, J. Slingerland, W. D. Foulkes

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Purpose: Decreased levels of the cyclin-dependent kinase inhibitor p27Kip1 in breast cancer are associated with a poor outcome. the prognostic significance of BRCA1/2 mutations is less clear, and the relationship between BRCA1/2 mutation status, p27Kip1 protein levels, and outcome has not been studied. Patients and Methods: Pathology blocks from 202 consecutive Ashkenazi Jewish women with primary invasive breast cancer were studied. Tumor DNA was tested for the three common BRCA1/2 founder mutations present in Ashkenazi Jews, and p27Kip1 expression was evaluated by immunohistochemistry. The median follow-up was 6.4 years. Results: Thirty-two tumors (16%) were positive for a BRCA1/2 mutation. Low p27Kip1 expression was seen in 110 tumors (63%) and was significantly associated with BRCA1/2 mutations (odds ratio, 4.0; 95% confidence interval [Cl], 1.4 to 11.1; P = .009). BRCA1/2 mutation carriers had a significantly worse 5-year distant disease-free survival (DDFS) compared with women without BRCA1/2 mutations (58% v 82%; P = .003). Similar results were seen for women whose tumors expressed low levels of p27Kip1, compared with those with high levels (5-year DDFS, 68% v 93% P < .0001). In a multivariate analysis, both BRCA1/2 mutation and low p27Kip1 expression were associated with a shorter DDFS (relative risk [RR], 2.1; 95% Cl, 1.0 to 4.3; P = .05; and RR, 3.9; 95% Cl, 1.4 to 11.1; P = .01, respectively). Conclusion: In this study, we showed that BRCA1/2 mutations were associated with low levels of p27Kip1 in breast cancer. Both BRCA1/2 and p27Kip1 status were identified as independent prognostic factors.

Original languageEnglish (US)
Pages (from-to)4045-4052
Number of pages8
JournalJournal of Clinical Oncology
Volume18
Issue number24
DOIs
StatePublished - Dec 15 2000
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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