The identification of steroid receptors in human breast cancer tissues has provided biochemical markers to predict hormone responsiveness. Analysis of tumors from 328 patients for the estrogen receptor protein (ERP) revealed significant levels in 225 patients (68%). Fifty-five patients with advanced disease were subjected to hormonal manipulation. Thirty patients underwent ablative surgery consisting of adrenalectomy or adrenalectomy and oophorectomy. Twenty-five patients were treated with additive therapy utilizing the new antiestrogen Tamoxifen. The ECOG criteria for an objective response were applied to all patients. Fifteen of the 24 estrogen receptor-positive patients (63%) subjected to endocrine ablation responded. Eleven of twenty (55%) ERP-positive patients responded to Tamoxifen therapy. Only one ERP-negative patient responded in the total group. Simultaneous analysis of these same specimens for the progesterone receptor protein (PgRP) revealed that 151 patients were ERP and PgRP positive (46%); 74 (23%) were ERP positive and PgRP negative; 90 (27%) were ERP and PgRP negative, and 13 (4%) were ERP negative and PgRP positive. In the two treatment groups the overall response rate when both receptors were positive was 77% with a higher percentage of responders in the endocrine ablative group (88% vs. 64%). In addition, a greater duration of response was achieved in those patients treated with endocrine ablation.