Amplification of DNA Topoisomerase II and c-erbB2 in Human Breast Cancer

Elevations of the c-erbB2 oncogene occur in about 30 of human breast cancers. Patients whose tumors show elevation of the c-erbB2 oncogene respond to anti-cancer drugs targeted against DNA topoisomerase II topo II. The gene for topo II is closely linked to the gene for c-erbB2 on chromosome 17. Laboratory data suggest that co-amplification of topo II with c-erbB2 occurs and renders tumor cells sensitive to drugs targeting topo II. This suggests that the reason patients with breast cancers showing amplification of c-erbB2 respond to topo II anticancer drugs is because of the co-amplification of topo II. This study used a novel quantitative polymerase chain reaction PCR method to determine the frequency of topo II and c-erbB2 gene amplification in samples of human breast cancer. Of 31 cases of breast cancer which showed c-erbB2 gene amplification by PCR, only 3 showed co-amplification of topo II. Therefore, co-amplification of both genes in human breast cancer is not a common event and probably does not explain the sensitivity of such tumors to topo II drug therapy. Alternatively, we observed high topo II protein expression in c-erbB2 amplified tumors. This most likely reflects the high number of proliferating cells in these tumors and may be the explanation for the sensitivity to topo II drugs.