Tamoxifen (NSC-180973, ICI-46474), an antiestrogen, was administered to 39 women with stage IV breast cancer at a dose of 20 mg orally every 12 hours. Patients were selected as eligible for endocrine ablative treatment and with disease not so aggressive as to jeopardize further treatment in case the experimental drug failed. Objective remission was obtained in 19 patients (49%) with a mean duration of 11+ months and ten patients are still in remission. No progression was seen in seven patients (18%) lasting 13+ months with only one patient in relapse. Thirteen patients (33%) have failed. Objective remission was obtained in two premenopausal women even though menstrual cycles were not suppressed; bilateral oophorectomy in one of these patients induced a second remission after relapse from tamoxifen. Objective remissions were obtained in two women with proven complete hypophysectomy a direct action of antiestrogens at the tumor level. Positive estrogen receptors were suggestive of being a good predictor of response. Menopausal status and dominant site of metastasis did not affect the response to tamoxifen in this small series. Tamoxifen did not alter prolactin secretion, and side effects from the drug were usually mild and transient in nature. We conclude that tamoxifen is an effective antitumor agent in patients with stage IV breast cancer; further studies are necessary to determine whether it will equal the therapeutic effect of oophorectomy, adrenalectomy, and hypophysectomy.
PIP: Preliminary results with the use of tamoxifen in 51 27-80 year old women with Stage 4 breast cancer are presented. There were 39 patients otherwise suitable for endocrine ablative procedures and 12 who had previously had such surgery. Tamoxifen was given in doses of 20 mg orally every 12 hours. Of the 39 patients, 19 had objective remissions with a mean duration of over 11 months. 7 others had no progression of their disease for over 13 months. Of 11 patients shown to have estrogen receptors, 6 showed remissions with the antiestrogen therapy. Objective remissions were obtained in 2 premenopausal women even though menopausal cycles were not suppressed. Bilateral oophorectomy in 1 of them later induced a 2nd remission. Objective remissions were obtained in 2 women with previous complete hypophysectomy. Serum prolactin levels in 8 patients studied were not changed by tamoxifen therapy. Side effects from the drug were mild and transitory. Results obtained with tamoxifen are approaching those obtained with endocrine ablative therapy. Further studies are needed to determine if endocrine ablation can induce further significant improvement beyond that which can be obtained with antiestrogen therapy.