Analysis of Oncogenes and Tumor Suppressor Genes in Human Breast Cancer

Oncogenes (c- erb B-2, c- myc , and some genes linked to the 11q13 lesion), tumor suppressor genes (retinoblastoma gene, p53) and an antimetastatic gene ( nm 23/nucleoside diphosphate kinase) play important roles in breast cancer progression. Amplification of c- erb B-2, c- myc , and int -2, and expression of RB, p53 (mutant), and NDP kinase were determined in 77 primary breast cancer specimens. nm 23-H1 allelic loss was also studied. c- erb B-2 and c- myc amplification, loss of RB expression, p53(mutant) expression, and nm 23-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- erb B-2 amplification was strongly associated with disease-free and overall survival in multivariate analysis ( P =0.002). All of the c- erb B-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.