Clinical Cancer Research, Vol 2, Issue 7 1177-1184, Copyright © 1996 by American Association for Cancer Research

ARTICLES

Cyclin DI amplification is not associated with reduced overall survival in primary breast cancer but may predict early relapse in patients with features of good prognosis

R Seshadri, CS Lee, R Hui, K McCaul, DJ Horsfall and RL Sutherland
Departments of Haematology and Surgery, Flinders Medical Centre, Bedford Park, South Australia 5042.

Amplification of chromosome 11q13 is frequently observed in human malignancies, including breast cancers. A candidate oncogene at this locus is the CCND1 gene, which encodes the cell cycle regulatory protein cyclin D1. Because published data on the relationship between 11q13 amplification and prognosis in breast cancer have been controversial, we investigated the clinical significance of CCND1 amplification and its association with established clinicopathological features of prognosis in 1014 primary breast cancer patients. Amplification of the CCND1 gene and the INT-2/FGF-3 gene, which also maps to 11q13, was 10% and 17%, respectively. There were no associations between CCND1 or INT-2 amplification and patient age, tumor size, tumor grade, axillary lymph node status, HER/neu amplification, MIB-1 monoclonal antibody to Ki67 antigen count, or p53 expression. CCND1 amplification was predominantly observed in hormone receptor-positive tumors; at a copy number >/=3, CCND1 amplification was significantly correlated with both estrogen receptor (ER; P = 0.036) and progesterone receptor (P = 0.012) positivity. After a median follow-up period of 66 months, CCND1 or INT-2 amplification was not associated with significant increases in relapse or death from breast cancer. However, in the node-negative and ER-positive subgroups, there was a trend for an increased relapse rate in patients with INT-2 or CCND1 amplification. Thus, in this study, assessment of CCND1 or INT-2 amplification at 11q13 by slot-blot hybridization was of little use in determining phenotype or disease outcome in the whole group of patients but had a potential role in identifying a subset of poor-prognosis patients within the node-negative or ER-positive, good-prognosis groups. Because the prevalence of CCND1 amplification is much lower than the reported prevalence of cyclin D1 overexpression, additional studies are required to determine the true prognostic significance of altered cyclin D1 expression in breast cancer.

This article has been cited by other articles:

				R. L. Kilker and M. D. Planas-Silva Cyclin D1 Is Necessary for Tamoxifen-Induced Cell Cycle Progression in Human Breast Cancer Cells Cancer Res., December 1, 2006; 66(23): 11478 - 11484. [Abstract] [Full Text] [PDF]

				H. Kawakubo, E. Brachtel, T. Hayashida, G. Yeo, J. Kish, A. Muzikansky, P. D. Walden, and S. Maheswaran Loss of B-cell translocation gene-2 in estrogen receptor-positive breast carcinoma is associated with tumor grade and overexpression of cyclin d1 protein. Cancer Res., July 15, 2006; 66(14): 7075 - 7082. [Abstract] [Full Text] [PDF]

				A. J Butt, C. M McNeil, E. A Musgrove, and R. L Sutherland Downstream targets of growth factor and oestrogen signalling and endocrine resistance: the potential roles of c-Myc, cyclin D1 and cyclin E Endocr. Relat. Cancer, July 1, 2005; 12(Supplement_1): S47 - S59. [Abstract] [Full Text] [PDF]

				K. Al-Kuraya, P. Schraml, J. Torhorst, C. Tapia, B. Zaharieva, H. Novotny, H. Spichtin, R. Maurer, M. Mirlacher, O. Kochli, et al. Prognostic Relevance of Gene Amplifications and Coamplifications in Breast Cancer Cancer Res., December 1, 2004; 64(23): 8534 - 8540. [Abstract] [Full Text] [PDF]

				R. Hui, G. L. Finney, J. S. Carroll, C. S. L. Lee, E. A. Musgrove, and R. L. Sutherland Constitutive Overexpression of Cyclin D1 but not Cyclin E Confers Acute Resistance to Antiestrogens in T-47D Breast Cancer Cells Cancer Res., December 1, 2002; 62(23): 6916 - 6923. [Abstract] [Full Text] [PDF]

				S. L. Holley, G. Parkes, C. Matthias, U. Bockmuhl, V. Jahnke, K. Leder, R. C. Strange, A. A. Fryer, and P. R. Hoban Cyclin D1 Polymorphism and Expression in Patients with Squamous Cell Carcinoma of the Head and Neck Am. J. Pathol., November 1, 2001; 159(5): 1917 - 1924. [Abstract] [Full Text] [PDF]

				L. J. Rush, Z. Dai, D. J. Smiraglia, X. Gao, F. A. Wright, M. Fruhwald, J. F. Costello, W. A. Held, L. Yu, R. Krahe, et al. Novel methylation targets in de novo acute myeloid leukemia with prevalence of chromosome 11 loci Blood, May 15, 2001; 97(10): 3226 - 3233. [Abstract] [Full Text] [PDF]

				R. G. Pestell, C. Albanese, A. T. Reutens, J. E. Segall, R. J. Lee, and A. Arnold The Cyclins and Cyclin-Dependent Kinase Inhibitors in Hormonal Regulation of Proliferation and Differentiation Endocr. Rev., August 1, 1999; 20(4): 501 - 534. [Abstract] [Full Text] [PDF]

				F. S. Kenny, R. Hui, E. A. Musgrove, J. M.W. Gee, R. W. Blamey, R. I. Nicholson, R. L. Sutherland, and J. F. R. Robertson Overexpression of Cyclin D1 Messenger RNA Predicts for Poor Prognosis in Estrogen Receptor-positive Breast Cancer Clin. Cancer Res., August 1, 1999; 5(8): 2069 - 2076. [Abstract] [Full Text] [PDF]