Analysis of Oncogenes and Tumor Suppressor Genes in Human Breast Cancer

Oncogenes (c‐erbB‐2, c‐myc, and some genes linked to the 11q13 lesion), tumor suppressor genes (retinoblastoma gene, p53) and an antimetastatic gene (nm23/nucleoside diphosphate kinase) play important roles in breast cancer progression. Amplification of c‐erbB‐2, c‐myc, and int‐2, and expression of RB, p53 (mutant), and NDP kinase were determined in 77 primary breast cancer specimens. nm23‐H1 allelic loss was also studied. c‐erbB‐2 and c‐myc amplification, loss of RB expression, p53(mutant) expression, and nm23‐H1 allelic loss were also found in non‐invasive carcinoma, int‐2 amplification was significantly correlated with lymph node status (P=0.02) and a significant association was found between p53(mutant) expression and tumor size (P=0.04). c‐erbB‐2 amplification was strongly associated with disease‐free and overall survival in multivariate analysis (P=0.002). All of the c‐erbB‐2 amplified cases and all but one of the int‐2 amplified cases in node‐positive patients had relapsed within 2 years post resection. The cancer cells may acquire new proliferative pathways sequentially as a result of multiple genetic alterations which enable them to bypass the estrogendependent proliferation.