Expression of cyclins E, A, and B, and prognosis in lymph node-negative breast cancer.

Unexpected outcomes in breast cancer demand a refinement of prognostic criteria. This study therefore investigated the prognostic relevance of cyclin expression in a cohort of 332 T1-T2 N0 infiltrating ductal carcinomas with long-term follow-up (median 99 months). By univariate analysis, tumour size, histopathological grade, hormone receptor content, cyclin E, cyclin B, and the Ki-S5 (Ki-67) index significantly predicted disease-specific and metastasis-free survival. Cyclin A did not achieve statistical significance. In a multivariate analysis, both cyclin E [relative risk (RR) 2.01, p = 0.021] and cyclin B (RR 1.85, p = 0.033) were selected as independent prognosticators of metastasis-free survival when the Ki-67 index was omitted, but only cyclin E expression was associated with disease-specific survival (RR 2.56, p = 0.006). When Ki-67 was included as a covariate, cyclin E lost its significance with respect to disease-specific survival but remained significant for metastasis-free survival. In an analogous analysis including Ki-67, the number of concurrently overexpressed cyclins did not attain statistical significance regarding disease-specific survival but was selected as the leading predictor of metastatic disease. It is concluded that combined overexpression of cyclins may imply genetic instability enhancing metastatic potential, but that survival ultimately depends on the proliferative activity of tumour cells. Copyright 2003 John Wiley & Sons, Ltd.