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A randomized clinical trial of nafoxidine, a non-steroidal oestrogen antagonist, and ethinyloestradiol in postmenopausal patients with advanced breast cancer produced objective remissions in 31% of 49 women receiving nafoxidine and in 14% of 49 receiving ethinyloestradiol. The differences in remission rates was almost significant (0.05 less than P less than 0.10). Life-threatening complications were more frequent with ethinyloestradiol than with nafoxidine but the latter produced specific toxic reactions on skin and hair that may limit its practical usefulness. Synthetic oestrogen antagonists may occupy a privileged place in the treatment of breast cancer, and other representatives of this new class of compounds should be accurately assessed in randomized clinical trials.

Rebound regression occurred in 13 of 42 females (30.9% with metastasising carcinoma of the breast in the postmenopausal period in whom additional hormonal treatment with ethinyl oestradiol had brought about a remission. Duration of the rebound response ranged from 3 to 44 months (average 11.2 months; mean 8 months). There was a significantly longer duration of remission (18.7 months compared with 12.0 months; P = 0.01) in patients with than those without a rebound response. There was also a significant correlation between the duration of the preceding remission under additional hormonal treatment and the duration of the subsequent rebound response (P less than 0.01). On the other hand, there was a negative but not significant correlation between the free interval duration which preceded the metastasisation and the duration of the rebound regression.

Human breast cancer was studied by in vitro techniques on tissue slices and extracts for a specific binding of estradiol and dihydrotestosterone. Estradiol receptors were found in 50 percent of patients in the premenopausal group and in 47 percent of patients in the postmenopausal group. The incidence of receptors in patients with metastatic disease was 32.5 percent. In 18 of 35 patients who were positive for receptor sites a remission was observed after a variety of endocrine treatment regimens. In contrast only 3 patients out of 43 with a negative binding pattern responded to treatment with nafoxidine for a very short time. The best correlation was found in the ovariectomized group. Between the responders and the nonresonders there is no difference in the quantitative receptor content. The same is valid in view of the duration of the remission.

L-Dopa lowers plasma prolactin levels, and there have been reports that patients with advanced breast cancer have been successfully treated with L-dopa. To test the potential value of L-dopa in this disease a randomized clinical trial of L-dopa and nafoxidine (as the reference compound) was conducted in postmenopausal women with advanced breast cancer. Objective remissions were obtained in sever out of 36 patients (19%) treated with nafoxidine but in none out of 40 patients treated with L-dopa. L-Dopa in the dose schedule used seems to be ineffective in advanced breast cancer.