A Randomized Trial Comparing Surgical Adrenalectomy with Aminoglutethimide plus Hydrocortisone in Women with Advanced Breast Cancer

We randomized 96 postmenopausal women with metastatic breast carcinoma to receive surgical adrenalectomy or medical therapy with an adrenal inhibitor, aminoglutethimide (AG), plus replacement hydrocortisone. Before randomization, women were stratified according to disease-free interval, site of dominant disease, and estrogen-receptor status. Of 40 evaluable women treated with AG and hydrocortisone, 53 per cent had objective responses, as compared with 45 per cent of 29 women undergoing surgical adrenalectomy (P value not significant). Responses lasted a mean of 17.2 months in the medical group and >17.1 months in the surgical group (not significant). Estrogen levels fell similarly in response to either treatment, whereas AG and hydrocortisone preserved androgen production. A null hypothesis tested the single question asked by this study:“Is surgical adrenalectomy superior to treatment with AG and hydrocortisone?”Rejection at significance levels of P = 0.01 and P = 0.07 for differences of 20 per cent and 10 per cent, respectively, suggested that medical therapy with AG and hydrocortisone may be logically chosen in place of surgical adrenalectomy. (N Engl J Med. 1981,; 305:545–51.) FIFTY to 60 per cent of postmenopausal women with estrogen-receptor-positive metastatic breast cancers have an objective response to surgical ablation of the adrenal or pituitary glands.^{1 2 3} However, the considerable morbidity and occasional mortality associated with these operations limit their use to highly selected patients.^{4 5 6} Consequently, several investigative groups have attempted to develop medical alternatives to surgical ablative therapy. They hypothesized that adrenalectomy and hypophysectomy cause tumor regression primarily by lowering estrogen production. Two separate medical strategies emanated from these studies: interference with hormone action through the use of antiestrogens^7,8 and inhibition of estrogen synthesis with enzyme antagonists.⁹ The latter approach. . .