title: 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.
abstract: 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.
authors.affiliation: Departments of Haematology and Surgery, Flinders Medical Centre, Bedford Park, South Australia 5042.
authors.forename: R
authors.initials: R
authors.lastname: Seshadri
authors.forename: C S
authors.initials: CS
authors.lastname: Lee
authors.forename: R
authors.initials: R
authors.lastname: Hui
authors.forename: K
authors.initials: K
authors.lastname: McCaul
authors.forename: D J
authors.initials: DJ
authors.lastname: Horsfall
authors.forename: R L
authors.initials: RL
authors.lastname: Sutherland
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002880:Chromosomes, Human, Pair 11; D019938:Cyclin D1 / Q000235:genetics*; D005260:Female; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis
chemical_list: C496444:FGF3 protein, human; D051518:Fibroblast Growth Factor 3; D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; D019938:Cyclin D1; D005346:Fibroblast Growth Factors