Biochemical basis for the antagonism between aminoglutethimide and danazol in the endocrine treatment of breast cancer.

Only 13% of postmenopausal advanced breast cancer patients responded to endocrine treatment with aminoglutethimide plus danazol whilst 33% responded to aminoglutethimide alone, despite a similar suppression of serum oestradiol levels in the two groups. The patients on aminoglutethimide and danazol showed a marked suppression of sex hormone binding-globulin binding capacity and a consequent rise in percent-free oestradiol. This led to the concentration of free oestradiol being less well suppressed than that of total oestradiol and in some patients free oestradiol concentrations were higher on treatment than before. Patients on aminoglutethimide alone showed no change in the binding of oestradiol and the percentage suppression of the free oestradiol concentration was similar to that of total oestradiol. The opposing effects of danazol and aminoglutethimide on the concentration of the free, biologically active fraction of oestradiol in the circulation may explain the poor therapeutic efficacy of this combination in breast cancer patients.