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 estrogen-dependent proliferation.