[Experimental multihormone therapy on human breast carcinomas grown in nude mice].
Experimental multihormone therapy with tamoxifen (TAM), aminoglutethimide (AMG) and medroxyprogesterone acetate (MPA) was investigated using three hormone-dependent human breast carcinomas serially transplanted into nude mice. TAM was the most effective of these agents, showing an efficacy rate of 100%, whereas MPA was the least effective, showing an efficacy rate of only 17%. The combination treatment of TAM and AMG was more effective than that of either TAM or AMG used alone. The antitumor effect of TAM was considered to be related to the changes of the hormone receptor levels. Since AMG significantly reduced the estrogen level and the uterine weight in normal female mice, the antitumor effect of combined TAM and AMG was assumed to be a result of the low estrogen level caused by AMG, enhancing the ability of TAM to compete with estrogen receptors. There was no additional antitumor effect of the combination of TAM and MPA, although serum MPA levels in mice were almost equivalent to those in humans who were treated with 1200mg of MPA po daily. These results indicated that combination hormone therapy, particularly with TAM and AMG, might be a promising method for the clinical treatment of human breast cancer.
Fukutomi
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Department of Surgery, School of Medicine, Keio University.
D000616:Aminoglutethimide / Q000008:administration & dosage*; D000818:Animals; D004359:Drug Therapy, Combination; D004967:Estrogens / Q000502:physiology*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D008525:Medroxyprogesterone / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D011960:Receptors, Estrogen / Q000187:drug effects; D013629:Tamoxifen / Q000008:administration & dosage*
D004967:Estrogens; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000616:Aminoglutethimide; D008525:Medroxyprogesterone