Suppression of estrogens with Aminoglutethimide and hydrocortisone (medical adrenalectomy) as treatment of advanced breast carcinoma: A review

Abstract

Fifty to sixty percent of postmenopausal women with estrogen receptor positive metastatic breast cancer respond objectively to surgical ablation of the pituitary or adrenal glands. Several investigators have recently developed medical alternatives to surgical ablative therapy for these patients. This review describes one of these strategies, the inhibition of estrogen synthesis with the enzyme inhibitor aminoglutethimide (AG). Aminoglutethimide blocks several cytochrome P-450-mediated steroid hydroxylation steps including those required for cholesterol to pregnenolone conversion and for the aromatization of androgens to estrogens. In women with metastatic carcinoma, a regimen including 1,000 mg of AG and 40 mg of hydrocortisone as replacement glucocorticoid was administered daily. Clinical studies revealed a 32% objective response rate to AG-HC in unselected patients, and a 52% response in women with estrogen receptor positive tumors. Randomized trials revealed that AG-HC produced objective regression as frequently as surgical adrenalectomy (Ag-HC + 53% vs. surgical adrenalectomy (43%,p = NS), and as surgical hypophysectomy (AG-HC 47% vs. hypox 21%,p + NS). Comparison of AG-HC administration with antiestrogen treatment suggested an equal rate of response to either therapy. Preliminary data document responses to AG in antiestrogen-resistant patients. Current studies do not allow precise recommendations regarding the sequence of use of antiestrogens and AG-HC.