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p27(Kip1) is a predictive factor for tamoxifen treatment response but not a prognostic marker in premenopausal breast cancer patients.

Stendahl, Maria LU ; Björner, Sofie LU ; Wigerup, Caroline LU ; Jirström, Karin LU ; Jönsson, Per-Ebbe LU ; Stål, Olle and Landberg, Göran LU (2010) In International Journal of Cancer Apr 7. p.2851-2858
Abstract
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 (ER) and cyclin D1, and p27 downregulation was associated with high proliferation. There was no association between recurrence-free-survival... (More)
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 (ER) 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. (c) 2010 UICC. (Less)
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Contribution to journal
publication status
published
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in
International Journal of Cancer
volume
Apr 7
pages
2851 - 2858
publisher
John Wiley & Sons
external identifiers
  • wos:000284208400012
  • pmid:20201092
  • scopus:78249249610
ISSN
0020-7136
DOI
10.1002/ijc.25297
language
English
LU publication?
yes
id
c0d850f7-9562-49f8-92ab-b11dd62228fb (old id 1582554)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20201092?dopt=Abstract
date added to LUP
2010-04-07 14:07:45
date last changed
2018-06-03 04:32:39
@article{c0d850f7-9562-49f8-92ab-b11dd62228fb,
  abstract     = {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 (ER) 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&lt;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. (c) 2010 UICC.},
  author       = {Stendahl, Maria and Björner, Sofie and Wigerup, Caroline and Jirström, Karin and Jönsson, Per-Ebbe and Stål, Olle and Landberg, Göran},
  issn         = {0020-7136},
  language     = {eng},
  pages        = {2851--2858},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {p27(Kip1) is a predictive factor for tamoxifen treatment response but not a prognostic marker in premenopausal breast cancer patients.},
  url          = {http://dx.doi.org/10.1002/ijc.25297},
  volume       = {Apr 7},
  year         = {2010},
}