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, Joyce M Slingerland, W. D. Foulkes

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

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Cyclin-Dependent Kinase Inhibitor p27
Breast Neoplasms
Mutation
Disease-Free Survival
Neoplasms
Jews
Cyclin-Dependent Kinases
Multivariate Analysis
Immunohistochemistry
Odds Ratio
Confidence Intervals
Pathology

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chappuis, P. O., Kapusta, L., Bégin, L. R., Wong, N., Brunet, J. S., Narod, S. A., ... Foulkes, W. D. (2000). Germline BRCA1/2 mutations and p27Kip1 protein levels independently predict outcome after breast cancer. Journal of Clinical Oncology, 18(24), 4045-4052.

Germline BRCA1/2 mutations and p27Kip1 protein levels independently predict outcome after breast cancer. / Chappuis, P. O.; Kapusta, L.; Bégin, L. R.; Wong, N.; Brunet, J. S.; Narod, S. A.; Slingerland, Joyce M; Foulkes, W. D.

In: Journal of Clinical Oncology, Vol. 18, No. 24, 15.12.2000, p. 4045-4052.

Research output: Contribution to journalArticle

Chappuis, PO, Kapusta, L, Bégin, LR, Wong, N, Brunet, JS, Narod, SA, Slingerland, JM & Foulkes, WD 2000, 'Germline BRCA1/2 mutations and p27Kip1 protein levels independently predict outcome after breast cancer', Journal of Clinical Oncology, vol. 18, no. 24, pp. 4045-4052.
Chappuis PO, Kapusta L, Bégin LR, Wong N, Brunet JS, Narod SA et al. Germline BRCA1/2 mutations and p27Kip1 protein levels independently predict outcome after breast cancer. Journal of Clinical Oncology. 2000 Dec 15;18(24):4045-4052.
Chappuis, P. O. ; Kapusta, L. ; Bégin, L. R. ; Wong, N. ; Brunet, J. S. ; Narod, S. A. ; Slingerland, Joyce M ; Foulkes, W. D. / Germline BRCA1/2 mutations and p27Kip1 protein levels independently predict outcome after breast cancer. In: Journal of Clinical Oncology. 2000 ; Vol. 18, No. 24. pp. 4045-4052.
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title = "Germline BRCA1/2 mutations and p27Kip1 protein levels independently predict outcome after breast cancer",
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.",
author = "Chappuis, {P. O.} and L. Kapusta and B{\'e}gin, {L. R.} and N. Wong and Brunet, {J. S.} and Narod, {S. A.} and Slingerland, {Joyce M} and Foulkes, {W. D.}",
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T1 - Germline BRCA1/2 mutations and p27Kip1 protein levels independently predict outcome after breast cancer

AU - Chappuis, P. O.

AU - Kapusta, L.

AU - Bégin, L. R.

AU - Wong, N.

AU - Brunet, J. S.

AU - Narod, S. A.

AU - Slingerland, Joyce M

AU - Foulkes, W. D.

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Y1 - 2000/12/15

N2 - 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.

AB - 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.

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