Prognostic significance of cyclin D1 overexpression in patients (pts) with primary breast cancer (BC)

Abstract

9714 Background: Cyclin D1, a key cell cycle regulator, is overexpressed in approximately 50% of BCs. Previous studies yielded conflicting results on the prognostic importance of cyclin D1 in BC. In this study, we evaluated overexpression of cyclin D1 in primary BC to determine any relation to clinicopathologic factors and its impact on survival. Methods: Formalin fixed tissue samples from 119 pts diagnosed with primary BC in 1996 and 1997 were analyzed for cyclin D1 expression by immunohistochemistry (IHC). A scoring system based on intensity and proportion of staining cells was used to judge cyclin D1 overexpression. ER, PR, Her2-Neu, p53 and Ki-67 expression by IHC and nuclear grade (NG) and histologic grade were determined at the time of diagnosis. OS and DFS curves were estimated by the method of Kaplan-Meier using log rank statistics. Clinicopathologic variables were included in Cox proportional hazards model to determine significance. Results: Cyclin D1 overexpression was observed in 68 of the 119 pts (57%). There was a positive correlation between cyclin D1 overexpression and ER expression (p=0.005) and an inverse correlation between cyclin D1 overexpression and both TNM stage and tumor size (p=0.009 and 0.042). Median follow up was 57 months. In univariate analysis, younger age, nodal involvement and higher NG were associated with poorer DFS (p=0.016, 0.001 and 0.026) and OS (p<0.001, p=0.016 and 0.036). Cyclin D1 had no influence on DFS or OS regardless of the cut point used to define overexpression. Among the ER positive subgroup however, there was a trend for improved OS in pts with cyclin D1 negative tumors (p=0.08). In contrast, cyclin D1 expression did not influence OS in ER negative subset. When ER positive pts with ductal carcinoma histology were considered, cyclin D1 negativity was associated with a better prognosis (p=0.053). In multivariate analyses of DFS and OS, only the nodal status (p=0.031 and 0.023) and NG (p=0.029 and 0.039) remained statistically significant. Conclusions: Cyclin D1 overexpression is not an independent predictor of prognosis in BC. In ER positive subgroup however, there is a trend for improved survival in cyclin D1 negative pts. No significant financial relationships to disclose.