Transgenic female mice carrying the V-Ha-ras transgene linked to the MMTV promoter, which developed mammary
carcinomas, were treated with selected
cancer chemotherapy drugs. Agents were administered i.p. on a daily x 9 schedule when mice developed
tumors that were 50-100 mg in size. Drugs which are clinically effective against
breast cancer were quite efficacious in the transgenic model at their maximum tolerated dose.
Doxorubicin produced excellent responses in
tumor-bearing transgenic mice, with several mammary
carcinomas undergoing
tumor shrinkage. Two anthrapyrazoles,
DuP 937 and
DuP 941, novel anticancer drugs with phase 2 activity against
breast cancer, were as effective as
doxorubicin in the oncomice.
Mitoxantrone, a synthetic agent with some properties similar to the
anthracyclines, also had antitumor activity, but not as pronounced as obtained with
doxorubicin or the anthrapyrazoles.
Cisplatin, a
drug with limited use in human
breast cancer, only caused modest antitumor responses. A computerized data analysis method based on the area under the
tumor growth curve was developed to better quantitate the data and provide statistical information. This quantitative analysis confirmed the high statistical significance of the activity of
doxorubicin or the anthrapyrazoles in the ras transgenic model, and defined an excellent dose response relationship for each
drug tested. Our results suggest that the ras transgenic model may be useful for identifying drugs that have efficacy for
breast cancer in women.