BIOLOGY AND THERAPEUTIC RESPONSE OF A MOUSE MAMMARY ADENOCARCINOMA (16-C) AND ITS POTENTIAL AS A MODEL FOR SURGICAL ADJUVANT CHEMOTHERAPY

Abstract

A mammary adenocarcinoma (16/C) was isolated and maintained in serial passage by transplantation of metastatic lung foci. This tumor originated as a spontaneous mammary adenocarcinoma in a C3H/He female mouse. It was selected as a model from > 50 mammary tumors studied because it was highly metastatic and because it responded to most of the agents reported to be active against breast cancer in women. S.c. implanted 16/C tumors (in the 300-1000 mg range) metastasized to the lungs in > 75% of the mice and to the axillary lymph nodes in > 30%. This tumor was tested for sensitivity to > 40 clinically used agents. Adriamycin was the most active single agent. Other active agents included cyclophosphamide, 5-fluorouracil, vincristine, melphalan, dibromodulcitol, maytansine, neocarzinostatin, palmO-ara-C [1-.beta.-D-arabinofuranosylcytosine 5''-palmitate], vinblastine and VP-16-213 [4''-demethylepipodophylloxin ethylidene-.beta.-D-glucopyranoside]. Agents most active against 40-1000 mg tumors were also most active against micrometastatic disease (e.g., adriamycin). The converse was also true; agents inactive or marginally active against 40-100 mg tumors were at best marginally active against micrometastatic disease, e.g., BCNU [1,3-bis(2-chloroethyl-1-nitrosourea)]. Tumors > 20 mg were not curable by chemotherapy alone, although adriamycin treatment caused complete regressions of 100-400 mg tumors in < 80% of the mice. Surgical removal of 300-1000 mg tumors plus therapy with adriamycin resulted in 40-72% cures as compared to 0-26% cures with surgery only. Data resulting from treatment with other agents, singly and in combination, were presented.