title: p27Kip1 is a predictive factor for tamoxifen treatment response but not a prognostic marker in premenopausal breast cancer patients.
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 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.
authors.affiliation: Center for Molecular Pathology, Lund University, Malmö University Hospital, Malmö, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Stendahl
authors.forename: Sofie
authors.initials: S
authors.lastname: Nilsson
authors.forename: Caroline
authors.initials: C
authors.lastname: Wigerup
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.forename: Per Ebbe
authors.initials: PE
authors.lastname: Jönsson
authors.forename: Olle
authors.initials: O
authors.lastname: Stål
authors.forename: Göran
authors.initials: G
authors.lastname: Landberg
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008875:Middle Aged; D017697:Premenopause; D011960:Receptors, Estrogen / Q000378:metabolism; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011960:Receptors, Estrogen; D013629:Tamoxifen; D050760:Cyclin-Dependent Kinase Inhibitor p27