Aromatase inhibitors and the treatment of breast cancer.

A M Brodie, L Y Wing, P Goss, M Dowsett, R C Coombes

文献索引：J. Steroid Biochem. 24 , 91, (1986)

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摘要

Inhibition of aromatase to reduce estrogen production by peripheral and ovarian tissue could be a useful approach to treating hormone-dependent breast cancer. Several C19, 17 keto steroids have been identified as aromatase inhibitors. The most potent of these cause rapid competitive inhibition followed by enzyme inactivation. Injections of the compounds caused inhibition of peripheral aromatization in monkeys. In rats, these treatments result in inhibition of ovarian aromatase and estrogen secretion, accompanied by marked regression of carcinogen(DMBA or NMU)-induced mammary tumors. To date, 60 postmenopausal patients with advanced metastatic breast cancer and unselected for the presence of estrogen receptors have been treated with once weekly injections of 4-OHA. The mean estradiol level measured in 14 patients was significantly reduced to 36% of pretreatment values after 1 month and remained at this level for up to 4 months. There was no effect of treatment on gonadotropin levels. Although all patients had relapsed from previous therapy, complete or partial tumor regression occurred in 30% of patients while 15% had static disease. The results indicate that in these patients the responses are due to inhibition of peripheral aromatization and that 4-OHA may be of value in treating postmenopausal breast cancer.