Cyclin A and E2F1 Overexpression Correlate with Reduced Disease-free Survival in Node-negative Breast Cancer Patients

Abstract

Background: Available prognostic factors do not accurately identify node-negative breast cancer patients at high risk of disease recurrence and progression. Patients and Methods: Cyclin A and E2F1 expression levels were evaluated in 75 consecutive node-negative breast cancer patients with a median follow-up of 10 years. Both parameters were tested for correlation with all the available clinicopathological parameters and with the clinical evolution of the disease. Results: Cyclin A was overexpressed in 45.3% of patients and significantly related to large tumor size, high Ki67 and high E2F1 expression levels. No relationship was observed between cyclin A and tumor estrogen receptor (ER) status, grading or patient age. Seventeen patients relapsed within 5 years from diagnosis. Twelve (71%) of them showed cyclin A overexpression in comparison with 22 (38%) out of the 58 who did not relapse (p=0.02). Disease-free survival (DFS) was significantly shorter in patients with cyclin A-overexpressing tumors compared to non-overexpressing ones (p=0.01). DFS was also significantly longer in low vs. high Ki67 expression (p=0.003) and in low vs. high E2F1 expression (p=0.02). On multivariate analysis, the simultaneous high expression of all three parameters (cyclin A, Ki67 and E2F1) was a strong independent prognostic factor for shorter DFS (HR 13.4). Conclusion: These findings suggest that assessment of cyclin A and/or E2F1 expression levels, associated with Ki67, might be useful for a better prognostic evaluation of node-negative breast cancer patients and support the need for further studies to evaluate their suitability for use in the routine clinical management of these patients.