title: Cyclin A is a prognostic indicator in early stage breast cancer with and without tamoxifen treatment.
abstract: Overexpression of G1-S regulators cyclin D1 or cyclin A is frequently observed in breast cancer and is also to result in ligand-independent activation of oestrogen receptor in vitro. This might therefore, provide a mechanism for failure of tamoxifen treatment. We examined by immunohistochemical staining the effect of deregulation of these, and other cell cycle regulators on tamoxifen treatment in a group of 394 patients with early stage breast cancer. In univariate analysis, expression of cyclin A, Neu, Ki-67 index, and lack of OR expression were significantly associated with worse prognosis. When adjusted by the clinical model (for lymph node status, age, performance status, T-classification, grade, prior surgery, oestrogen receptor status and tamoxifen use), only overexpression of cyclin A and Neu were significantly associated with worse prognosis with hazard ratios of, respectively, 1.709 (P=0.0195) and 1.884 (P=0.0151). Overexpression of cyclin A was found in 86 out of the 201 OR-positive cases treated with tamoxifen, and was the only independent marker associated with worse prognosis (hazard ratio 2.024, P=0.0462). In conclusion, cyclin A is an independent predictor of recurrence of early stage breast cancer and is as such a marker for response in patients treated with tamoxifen.
authors.affiliation: Division of Tumour Biology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. rmichal@nki.nl
authors.forename: R
authors.initials: R
authors.lastname: Michalides
authors.forename: H
authors.initials: H
authors.lastname: van Tinteren
authors.forename: A
authors.initials: A
authors.lastname: Balkenende
authors.forename: J B
authors.initials: JB
authors.lastname: Vermorken
authors.forename: J
authors.initials: J
authors.lastname: Benraadt
authors.forename: J
authors.initials: J
authors.lastname: Huldij
authors.forename: P
authors.initials: P
authors.lastname: van Diest
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002453:Cell Cycle; D019925:Cyclin A / Q000032:analysis*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D019925:Cyclin A; D011960:Receptors, Estrogen; D013629:Tamoxifen