Assessing sequential oncogene amplification in human breast cancer

Studies of amplification and/or overexpression of c‐myc, HER‐2/neu, and H‐ras in breast cancer have shown that each is associated with a poor prognosis. The purpose of this study was to explore the possibility that there is a preferred sequence of amplification of these oncogenes in breast cancer. The frequencies of amplification and patterns of co‐amplification of c‐myc, HER‐2/neu, and H‐ras were studied in a group of 84 breast cancers. The data suggested a preferred sequence of amplification that consisted of c‐myc amplification‐HER‐2/neu amplification‐H‐ras amplification. This model was supported by loglinear analysis. In addition, the levels of amplification of JC‐A, a DNA fragment newly isolated from a patient with advanced breast cancer, were studied in 61 of these cases. The data suggested that JC‐A amplification occurred early. Loglinear analysis supported a model in which JC‐A amplification occurred either before or after c‐myc amplification but was unrelated to Her‐2/neu or ras amplification. © 1995 Wiley‐Liss, Inc.