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p27 Kip1 is a predictive factor for tamoxifen treatment response but not a prognostic marker in premenopausal breast cancer patients
Author(s) -
Stendahl Maria,
Nilsson Sofie,
Wigerup Caroline,
Jirström Karin,
Jönsson Per Ebbe,
Stål Olle,
Landberg Göran
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25297
Subject(s) - tamoxifen , medicine , breast cancer , downregulation and upregulation , oncology , predictive marker , cyclin d1 , tissue microarray , cancer , cancer research , cell cycle , biology , biochemistry , gene
The cell‐cycle regulating protein p27 Kip1 (p27) has dual roles by acting as both a cdk inhibitor and as an assembly factor for different cdk complexes. Loss of p27 has been linked to malignant features in tumours; however, the exact role of p27 deregulation in breast cancer regarding prognostic and treatment predictive information has not been fully clarified. We have evaluated p27 expression in 328 primary, Stage II breast cancers from premenopausal patients who had been randomised to either tamoxifen treatment or no adjuvant treatment after surgery. p27 was associated with the oestrogen receptor and cyclin D1, and p27 downregulation was associated with high proliferation. There was no association between recurrence‐free survival (RFS) and p27 (HR = 0.800, 95% CI 0.523–1.222, p = 0.300), indicating that p27 is not a prognostic marker. The predictive value of p27 was analysed by comparing RFS in tamoxifen‐treated and untreated patients in subgroups of low and high p27 expression (HR = 0.747, 95% CI 0.335–1.664, p = 0.474 and HR = 0.401, 95% CI 0.240–0.670, p < 0.001, respectively). Only patients with p27‐high tumours benefited from tamoxifen (multivariate interaction analysis p = 0.034). Our study suggests that p27 downregulation is associated with tamoxifen resistance in premenopausal breast cancer but is not linked to impaired prognosis.