CYCLIN D1 AMPLIFICATION IS NOT ASSOCIATED WITH REDUCED OVERALL SURVIVAL IN PRIMARY BREAST-CANCER BUT MAY PREDICT EARLY RELAPSE IN PATIENTS WITH FEATURES OF GOOD PROGNOSIS

Amplification of chromosome 11q13 is frequently observed in human mali gnancies, including breast cancers, A candidate oncogene at this locus is the CCND1 gene, which encodes the fell cycle regulatory protein cy clin D1. Because published data on the relationship between 11q13 ampl ification and prognosis in breast cancer have been controversial, we i nvestigated the clinical significance of CCND1 amplification and its a ssociation with established clinicopathological features of prognosis in 1014 primary breast cancer patients, Amplification of the CCND1 gen e 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 ampli fication and patient age, tumor size, tumor grade, axillary lymph node status, HER/neu amplification, MIB-1 monoclonal antibody to Ki67 anti gen count, or p53 expression, CCND1 amplification was predominantly ob served in hormone receptor-positive tumors; at a copy number greater t han or equal to 3, CCND1 amplification was significantly correlated wi th both estrogen receptor (ER; P = 0.036) and progesterone receptor (P = 0.012) positivity, After a median follow-up period of 66 months, CC ND1 or INT-2 amplification was not associated with significant increas es in relapse or death from breast cancer, However, in the node-negati ve and ER-positive subgroups, there was a trend for an increased relap se rate in patients with INT-2 or CCND1 amplification, Thus, in this s tudy, assessment of CCND1 or INT-2 amplification at 11q13 by slot-blot hybridization was of little use in determining phenotype or disease o utcome in the whole group of patients but had a potential role in iden tifying a subset of poor-prognosis patients within the node-negative o r 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 canc er.