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Effects of Endocrine Regulation of Growth of a Mouse Mammary Tumor on Its Sensitivity to Chemotherapy¹

Department of Anatomy, University of British Columbia, Vancouver, British Columbia V6T 1W5, Canada

Mice bearing the androgen-responsive Shionogi mammary carcinoma SC115 were treated with different concentrations of testosterone to determine if regulation of growth by testosterone would affect the susceptibility of the tumor to eradication by drugs. Following s.c. injection of 2 x 10⁶ cells, tumors grew to 3 g by 21 ± 2.1 days in males (n = seven) and 30 ± 2.4 days in females administered testosterone (n = ten). If androgen was withdrawn, tumors weighing 1 g regressed temporarily but resumed growing after a delay of 19 ± 1.7 days in males and 6 ± 3.2 days in females. A combination of cyclophosphamide (100 mg/kg) and Adriamycin (6.5 mg/kg), three i.p. injections 7 days apart, caused a tumor growth delay (TGD) of 5 ± 3.8 days in males and 26 ± 3.2 days in females. The combination of endocrine therapy and chemotherapy was superior to either treatment alone in males. Androgen withdrawal plus chemotherapy was additive; a submaximal dose of testosterone for tumor growth plus drugs was more effective, causing a TGD of 40 ± 2.7 days. There were no significant differences in TGD in females receiving treatments singly or in combination, possibly due to the fact that tumors in females were more sensitive to drugs alone and less sensitive to testosterone alone than were tumors in males. To ascertain if combination therapy would be effective in females in an adjuvant situation, the same treatment regimens were administered 1 day after injection of 10⁶ tumor cells. Under these conditions, hormonal manipulations combined with chemotherapy resulted in a longer TGD than either modality alone. Furthermore, submaximal doses of testosterone for growth plus chemotherapy induced a longer disease-free interval (no palpable tumors by 120 days in 12 of 12 mice) than did complete androgen withdrawal plus drugs (palpable tumors in 4 of 5 mice by 104 ± 2.7 days). The results demonstrate that endocrine regulation of SC115 mammary tumor growth can alter responsiveness of the tumor to chemotherapy.

¹ Supported by a grant from the National Cancer Institute of Canada. This work was initiated while J. T. E. was a visiting professor at the Department of Cancer Endocrinology, Cancer Control Agency of British Columbia, Vancouver, B.C., Canada.

² Research Scholar of the National Cancer Institute of Canada. To whom requests for reprints should be addressed.

Received 9/ 7/83. Accepted 12/14/83.

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