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J Steroid Biochem Mol Biol. 1992 Sep;43(1-3):149-53.

Inhibition of oestrogen synthesis in postmenopausal women with breast cancer.

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Unit of Metabolic Medicine, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, England.


The effectiveness in reducing oestrogen exposure, of an aromatase inhibitor, and a sulphatase inhibitor, as measured by in vivo studies in breast cancer patients, has been investigated. 4-Hydroxyandrostenedione (4HA) was shown to diminish plasma oestrogen levels, to inhibit peripheral and local aromatization and to cause a concomitant decrease in the activity of DNA-polymerase-alpha, measured as an indicator of cellular proliferation. The source of oestrone sulphate in breast tissues was examined, and it was shown that the tissue content of this conjugate derived from circulating oestrone, but no evidence could be found for the direct accumulation of conjugate from the plasma. Administration of Danazol was found to cause a fall in plasma oestrone levels, and to diminish the conversion ratio of oestrone sulphate to oestrone in some patients. It also inhibited tissue sulphatase activity. Although it is concluded that this drug is only a weak sulphatase inhibitor, these observations indicate the potential value of developing more efficient sulphatase inhibitors. Enzyme inhibition is now a proven effective treatment for breast cancer and the development of more efficient inhibitors is an important objective.

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