Overexpression of cyclinD1 predicts for poor prognosis in estrogen receptor‐negative breast cancer patients

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Abstract
CyclinD1 plays a critical role in regulating cell cycle progression. CyclinD1 mRNA and protein are overexpressed in approximately 50% of primary breast cancer cases. However, its clinical significance as a predictive factor remains unclear. One hundred and seventy‐three female patients diagnosed with invasive ductal carcinoma who had undergone a mastectomy (161 patients) or breast‐conserving surgery (12 patients) were followed up for 6–119 months (median 86 months) postoperatively. Immunoreactivity for monoclonal anti‐cyclinD1 antibody (clone DCS‐6) with paraffin‐embedded carcinoma tissues was investigated using a labeled streptavidin‐biotin method. Overexpression of cyclinD1 was found in 42% (73 of 173), and strongly correlated with estrogen receptor (ER) expression (p< 0.000001). Univariate analysis revealed no association between overexpression of cyclinD1 and overall survival or relapse‐free survival in all patient groups. However, in the ER‐negative subgroup (n= 75), overexpression of cyclinD1 was significantly correlated with shorter overall survival (p= 0.018) and relapse‐free survival (p= 0.014) as well as the lymph node status and tumor size. In contrast, there were no significant associations between overexpression of cyclinD1 and clinical outcome in the ER‐positive subgroup. According to Cox's multivariate analysis in the ER‐negative subgroup, overexpression of cyclinD1 had the most significant effect on overall survival (p= 0.02) and relapse‐free survival (p= 0.0058), followed by nodal status and histologic grade. These findings suggest that overexpression of cyclinD1 is an independent prognostic indicator in ER‐negative breast cancer patients.