This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pohl, G. Articles by Filipits, M. Search for Related Content PubMed PubMed Citation Articles by Pohl, G. Articles by Filipits, M. Social Bookmarking                            What's this?

High p27^Kip1 Expression Predicts Superior Relapse-Free and Overall Survival for Premenopausal Women With Early-Stage Breast Cancer Receiving Adjuvant Treatment With Tamoxifen Plus Goserelin

Gudrun Pohl, Margaretha Rudas, Otto Dietze, Sigurd Lax, Eva Markis, Robert Pirker, Christoph C. Zielinski, Hubert Hausmaninger, Ernst Kubista, Hellmut Samonigg, Raimund Jakesz, Martin Filipits

From the Departments of Medicine I, Pathology, Surgery, and Gynecology, University of Vienna, Vienna; the Department of Pathology and the Third Medical Department, Salzburg Hospital, Salzburg; the Department of Pathology and the Medical Department, University of Graz, Graz; and the Department of Pathology, Wiener Neustadt General Hospital, Wiener Neustadt, Austria.

Address reprint requests to Martin Filipits, PhD, Associate Professor, Department of Medicine I, Clinical Division of Oncology, University of Vienna, Waehringer Guertel 18–20, A-1090 Vienna, Austria; e-mail: martin.filipits{at}akh-wien.ac.at.

Purpose: To determine the predictive value of p27^Kip1 in premenopausal women with early-stage hormone receptor–positive breast cancer.

Patients and Methods: We retrospectively examined tumor specimens from 512 patients with breast cancer who were enrolled onto Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 5. In this trial, premenopausal, hormone receptor–positive breast cancer patients with stage I and II disease were randomly assigned to receive either 5 years of tamoxifen plus 3 years of goserelin or six cycles of cyclophosphamide, methotrexate, and fluorouracil. p27^Kip1 expression was assessed by immunohistochemistry, and its association with clinical outcome was determined. Statistical analyses were performed to test for interaction between p27^Kip1 status and treatment.

Results: High p27^Kip1 expression (nuclear p27^Kip1 staining in 50% of tumor cells) independently predicted superior relapse-free survival (RFS) and overall survival (OS) in both the total study population (RFS: relative risk [RR], 0.53; 95% CI, 0.34 to 0.82; P = .004; OS: RR, 0.29; 95% CI, 0.15 to 0.58; P < .001) and patients treated with combination endocrine therapy (RFS: RR, 0.32; 95% CI, 0.16 to 0.63; P = .001; OS: RR, 0.16; 95% CI, 0.05 to 0.53; P = .003). The interaction between p27^Kip1 expression and treatment was statistically significant for RFS (P = .04) but not for OS (P = .27).

Conclusion: High p27^Kip1 expression was an independent predictor of responsiveness to hormonal therapy and thus may be useful for the selection of premenopausal women with early-stage hormone receptor–positive breast cancer for adjuvant combination endocrine therapy.

Supported by the Austrian Science Fund (Hertha-Firnberg Fellowship T71-MED and a Grant Project P15377).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. E. Glover, K. E. Gurley, K.-H. Kim, B. Storer, M. L. Fero, and C. J. Kemp Endocrine dysfunction in p27Kip1 deficient mice and susceptibility to Wnt-1 driven breast cancer Carcinogenesis, June 1, 2009; 30(6): 1058 - 1063. [Abstract] [Full Text] [PDF]

				A. Ravaioli, F. Monti, M. M. Regan, F. Maffini, M. G. Mastropasqua, V. Spataro, M. Castiglione-Gertsch, I. Panzini, L. Gianni, A. Goldhirsch, et al. p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer Ann. Onc., April 1, 2008; 19(4): 660 - 668. [Abstract] [Full Text] [PDF]

				P. L. Porter, W. E. Barlow, I-T. Yeh, M. G. Lin, X. P. Yuan, E. Donato, G. W. Sledge, C. L. Shapiro, J. N. Ingle, C. M. Haskell, et al. p27Kip1 and Cyclin E Expression and Breast Cancer Survival After Treatment With Adjuvant Chemotherapy J Natl Cancer Inst, December 6, 2006; 98(23): 1723 - 1731. [Abstract] [Full Text] [PDF]

				M. Colozza, E. Azambuja, F. Cardoso, C. Sotiriou, D. Larsimont, and M. J. Piccart Proliferative markers as prognostic and predictive tools in early breast cancer: where are we now? Ann. Onc., November 1, 2005; 16(11): 1723 - 1739. [Abstract] [Full Text] [PDF]

				M. Filipits, G. Pohl, M. Rudas, O. Dietze, S. Lax, R. Grill, R. Pirker, C. C. Zielinski, H. Hausmaninger, E. Kubista, et al. Clinical Role of Multidrug Resistance Protein 1 Expression in Chemotherapy Resistance in Early-Stage Breast Cancer: The Austrian Breast and Colorectal Cancer Study Group J. Clin. Oncol., February 20, 2005; 23(6): 1161 - 1168. [Abstract] [Full Text] [PDF]

				C. L. Arteaga Cdk Inhibitor p27Kip1 and Hormone Dependence in Breast Cancer Clin. Cancer Res., January 1, 2004; 10(1): 368S - 371S. [Abstract] [Full Text] [PDF]