Cyclin A is a Prognostic Indicator in Early Stage Breast Cancer with and Without Tamoxifen Treatment

Overview

Journal Br J Cancer

Specialty Oncology

Date 2002 Mar 5

PMID 11875707

Citations 37

Authors

R Michalides

H van Tinteren

A Balkenende

J B Vermorken

J Benraadt

J Huldij

P van Diest

Affiliations

Soon will be listed here.

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.

Citing Articles

A retrospective analysis of clinicopathological characteristics and risk factors for recurrence in young patients with breast cancer.

Chen L, Chen Q, Zhu M Gland Surg. 2024; 13(7):1281-1290.

PMID: 39175705 PMC: 11336790. DOI: 10.21037/gs-24-193.

Hypermethylation of the Gene Body in Is Involved in Breast Cancer Cell Proliferation and Is a Potential Blood-Based Biomarker for Early Detection and a Poor Prognosis.

Shen H, Hung C, Davis C, Su C, Liao L, Shih H Biomolecules. 2024; 14(5).

PMID: 38785978 PMC: 11118508. DOI: 10.3390/biom14050571.

Inhibitors, PROTACs and Molecular Glues as Diverse Therapeutic Modalities to Target Cyclin-Dependent Kinase.

Rana S, Mallareddy J, Singh S, Boghean L, Natarajan A Cancers (Basel). 2021; 13(21).

PMID: 34771669 PMC: 8583118. DOI: 10.3390/cancers13215506.

Oncogenic and Tumor Suppressive Components of the Cell Cycle in Breast Cancer Progression and Prognosis.

Kashyap D, Garg V, Sandberg E, Goel N, Bishayee A Pharmaceutics. 2021; 13(4).

PMID: 33920506 PMC: 8072616. DOI: 10.3390/pharmaceutics13040569.

Identification and Verification of Biomarker in Clear Cell Renal Cell Carcinoma via Bioinformatics and Neural Network Model.

Liu B, Xiao Y, Li H, Zhang A, Meng L, Feng L Biomed Res Int. 2020; 2020:6954793.

PMID: 32626756 PMC: 7317307. DOI: 10.1155/2020/6954793.

References

Bukholm I, Bukholm G, Nesland J . Over-expression of cyclin A is highly associated with early relapse and reduced survival in patients with primary breast carcinomas. Int J Cancer. 2001; 93(2):283-7. DOI: 10.1002/ijc.1311. View

Sherr C, Roberts J . CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999; 13(12):1501-12. DOI: 10.1101/gad.13.12.1501. View

Cangi M, Cukor B, Soung P, Signoretti S, Moreira Jr G, Ranashinge M . Role of the Cdc25A phosphatase in human breast cancer. J Clin Invest. 2000; 106(6):753-61. PMC: 381390. DOI: 10.1172/JCI9174. View

Michalides R . Cell cycle regulators: mechanisms and their role in aetiology, prognosis, and treatment of cancer. J Clin Pathol. 2000; 52(8):555-68. PMC: 500945. DOI: 10.1136/jcp.52.8.555. View

Zwijsen R, Buckle R, Hijmans E, Loomans C, Bernards R . Ligand-independent recruitment of steroid receptor coactivators to estrogen receptor by cyclin D1. Genes Dev. 1998; 12(22):3488-98. PMC: 317237. DOI: 10.1101/gad.12.22.3488. View

. Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group. Lancet. 1998; 351(9114):1451-67. View

Prall O, Sarcevic B, Musgrove E, Watts C, Sutherland R . Estrogen-induced activation of Cdk4 and Cdk2 during G1-S phase progression is accompanied by increased cyclin D1 expression and decreased cyclin-dependent kinase inhibitor association with cyclin E-Cdk2. J Biol Chem. 1997; 272(16):10882-94. DOI: 10.1074/jbc.272.16.10882. View

Michalides R, Hageman P, van Tinteren H, Houben L, Wientjens E, Klompmaker R . A clinicopathological study on overexpression of cyclin D1 and of p53 in a series of 248 patients with operable breast cancer. Br J Cancer. 1996; 73(6):728-34. PMC: 2074376. DOI: 10.1038/bjc.1996.128. View

Lamb J, Ladha M, McMahon C, Sutherland R, Ewen M . Regulation of the functional interaction between cyclin D1 and the estrogen receptor. Mol Cell Biol. 2000; 20(23):8667-75. PMC: 86475. DOI: 10.1128/MCB.20.23.8667-8675.2000. View

10.

Bodrug S, Warner B, Bath M, Lindeman G, Harris A, Adams J . Cyclin D1 transgene impedes lymphocyte maturation and collaborates in lymphomagenesis with the myc gene. EMBO J. 1994; 13(9):2124-30. PMC: 395065. DOI: 10.1002/j.1460-2075.1994.tb06488.x. View

11.

Slamon D, Clark G, Wong S, Levin W, Ullrich A, McGuire W . Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235(4785):177-82. DOI: 10.1126/science.3798106. View

12.

de Jong J, van Diest P, Michalides R, Baak J . Concerted overexpression of the genes encoding p21 and cyclin D1 is associated with growth inhibition and differentiation in various carcinomas. Mol Pathol. 1999; 52(2):78-83. PMC: 395678. DOI: 10.1136/mp.52.2.78. View

13.

Barbareschi M, Pelosio P, Caffo O, Buttitta F, Pellegrini S, Barbazza R . Cyclin-D1-gene amplification and expression in breast carcinoma: relation with clinicopathologic characteristics and with retinoblastoma gene product, p53 and p21WAF1 immunohistochemical expression. Int J Cancer. 1997; 74(2):171-4. DOI: 10.1002/(sici)1097-0215(19970422)74:2<171::aid-ijc5>3.0.co;2-w. View

14.

Leong A, Hanby A, Potts H, Tan D, Skilton D, Ryder K . Cell cycle proteins do not predict outcome in grade I infiltrating ductal carcinoma of the breast. Int J Cancer. 2000; 89(1):26-31. DOI: 10.1002/(sici)1097-0215(20000120)89:1<26::aid-ijc5>3.0.co;2-8. View

15.

Cariou S, Donovan J, Flanagan W, Milic A, Bhattacharya N, Slingerland J . Down-regulation of p21WAF1/CIP1 or p27Kip1 abrogates antiestrogen-mediated cell cycle arrest in human breast cancer cells. Proc Natl Acad Sci U S A. 2000; 97(16):9042-6. PMC: 16818. DOI: 10.1073/pnas.160016897. View

16.

Cicatiello L, Addeo R, Altucci L, Belsito Petrizzi V, Boccia V, Cancemi M . The antiestrogen ICI 182,780 inhibits proliferation of human breast cancer cells by interfering with multiple, sequential estrogen-regulated processes required for cell cycle completion. Mol Cell Endocrinol. 2000; 165(1-2):199-209. DOI: 10.1016/s0303-7207(00)00243-4. View

17.

Elston C, Ellis I . Pathology and breast screening. Histopathology. 1990; 16(2):109-18. DOI: 10.1111/j.1365-2559.1990.tb01078.x. View

18.

Diehl J, Zindy F, Sherr C . Inhibition of cyclin D1 phosphorylation on threonine-286 prevents its rapid degradation via the ubiquitin-proteasome pathway. Genes Dev. 1997; 11(8):957-72. DOI: 10.1101/gad.11.8.957. View

19.

Jinno S, Suto K, Nagata A, Igarashi M, Kanaoka Y, Nojima H . Cdc25A is a novel phosphatase functioning early in the cell cycle. EMBO J. 1994; 13(7):1549-56. PMC: 394984. DOI: 10.1002/j.1460-2075.1994.tb06417.x. View

20.

van Diest P, Michalides R, Jannink L, van der Valk P, Peterse H, de Jong J . Cyclin D1 expression in invasive breast cancer. Correlations and prognostic value. Am J Pathol. 1997; 150(2):705-11. PMC: 1858273. View