HER-2/neu, c-Myc and cyclin-A in human breast cancer.

To better understand the role of HER-2/neu, c-myc and cyclin-A which seem to be activated in different steps of tumor cell growth, we analyzed a series of breast cancers from patients subjected to radical mastectomy with regard to HER-2/neu amplification (N=171) and expression of HER-2/neu (N=114), c-myc (N=31) and cyclin-A (N=71). Molecular evaluation demonstrated that HER-2/neu was amplified in 20% of cases and overexpressed in 27%, and its alterations were associated with a higher proliferative activity (H-3-Tdr-labeling index), although not statistically significant in patients without lymph node metastases, c-myc was overexpressed in 16% of cases and was weakly correlated to proliferation activity. Cyclin-A was overexpressed in 15% of cases and was significantly correlated to the percentage of the H-3-Tdr labeled cell fraction (p=0.002). Cyclin-A alterations were also significantly associated with well-differentiated tumors, suggesting that this gene could be involved in the control of the normal cell cycle rather than to cell proliferation during tumor growth.