Cyclin a is a novel modulator of tamoxifen treatment in early stage breast cancer

R. J A M Michalides, H. J. Van Tinteren, A. Balkenende, J. Vermorken, J. Benraadt, P. J. Van Diest

Research output: Contribution to journalArticle

Abstract

Deregulation of G1-S transition has frequently been observed in various tumours, including human breast cancer, and might well affect outcome of therapy. First choice of treatment of estrogen-receptor positive breast cancer is the anti-estrogen tamoxifen. However, in approximately 30% of these cases. tumour recurs despite treatment. Overexpression of G1-S regulators cyclin D1 or cyclin A has been reported to result in ligand-independent activation of estrogen receptor in vitro, and 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 (cyclin E, p53, p21, p27, Neu, epidermal growth factor receptor, Ki67, estrogen receptor (ER), progesterone receptor (PR), on tamoxifen treatment in a group of 394 patients with early stage breast cancer. In univariate analysis, expression of cyclin A, Neu, high Ki-67 index, and lack of ER 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, estrogen 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). In tamoxifen treated ER-positive tumours, overexpression of cyclin A was the only independent marker associated with a worse prognosis (Hazard Ratio 2.024, p= 0.0462). In conclusion, cyclin A is a novel independent predictor of response to tamoxifen treatment in early stage breast cancer.

Original languageEnglish (US)
Pages (from-to)244
Number of pages1
JournalBreast Cancer Research and Treatment
Volume69
Issue number3
StatePublished - 2001
Externally publishedYes

Fingerprint

Cyclins
Cyclin A
Tamoxifen
Estrogen Receptors
Breast Neoplasms
Therapeutics
Cyclin E
Neoplasms
Cyclin D1
Progesterone Receptors
Treatment Failure
Epidermal Growth Factor Receptor
Cell Cycle
Estrogens
Lymph Nodes
Staining and Labeling
Ligands

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Michalides, R. J. A. M., Van Tinteren, H. J., Balkenende, A., Vermorken, J., Benraadt, J., & Van Diest, P. J. (2001). Cyclin a is a novel modulator of tamoxifen treatment in early stage breast cancer. Breast Cancer Research and Treatment, 69(3), 244.

Cyclin a is a novel modulator of tamoxifen treatment in early stage breast cancer. / Michalides, R. J A M; Van Tinteren, H. J.; Balkenende, A.; Vermorken, J.; Benraadt, J.; Van Diest, P. J.

In: Breast Cancer Research and Treatment, Vol. 69, No. 3, 2001, p. 244.

Research output: Contribution to journalArticle

Michalides, RJAM, Van Tinteren, HJ, Balkenende, A, Vermorken, J, Benraadt, J & Van Diest, PJ 2001, 'Cyclin a is a novel modulator of tamoxifen treatment in early stage breast cancer', Breast Cancer Research and Treatment, vol. 69, no. 3, pp. 244.
Michalides RJAM, Van Tinteren HJ, Balkenende A, Vermorken J, Benraadt J, Van Diest PJ. Cyclin a is a novel modulator of tamoxifen treatment in early stage breast cancer. Breast Cancer Research and Treatment. 2001;69(3):244.
Michalides, R. J A M ; Van Tinteren, H. J. ; Balkenende, A. ; Vermorken, J. ; Benraadt, J. ; Van Diest, P. J. / Cyclin a is a novel modulator of tamoxifen treatment in early stage breast cancer. In: Breast Cancer Research and Treatment. 2001 ; Vol. 69, No. 3. pp. 244.
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