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Estrogen deprivation by aromatase inhibition is an effective treatment in breast cancer. Between October 1986 and March 1988, 91 postmenopausal patients with advanced breast cancer entered a phase II study performed jointly in three center to investigate the new aromatase inhibitor 4-hydroxyandrostenedione. Patients received 500 mg 4-hydroxyandrostenedione intramuscularly (IM) every 2 weeks for 6 weeks, and 250 mg every 2 weeks thereafter. There were two complete (CRs) and 19 partial remissions (PRs) (response rate, 23%). Disease stabilization (no change; NC) was seen in 26 patients, and in 44 patients (48%), disease progression occurred. Duration of the CRs is 20+ months, median durations of PR and NC are 13+ and 8 months, respectively. Receptor status, relapse-free interval, and sites of metastatic lesions did not appear to influence treatment results. However, efficacy of previous tamoxifen treatment favorably predicted response to 4-hydroxyandrostenedione. Serum estradiol levels decreased significantly in patients after 2 weeks of treatment. Side effects were mostly nonspecific and of low degree, requiring discontinuation of treatment in only 3% of the patients. We conclude that aromatase inhibition with 4-hydroxyandrostenedione is efficacious in the treatment of postmenopausal breast cancer.

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Methylspiperone, carfentanil, and suriclone, labeled with 11C, can be used in assessment of dopamine, mu-type opiate receptors, and benzodiazapine receptors in the brains of living human beings. These relatively specific neuronal probes permit measurement of the number and state of occupancy of receptors in the brain in health and disease, and may be useful to assess endogenous neurotransmitter secretion by decreasing competitive binding of the labeled ligand. To date, the most striking finding has been a decrease in the indices of dopamine and serotonin receptor densities as a function of age in normal men and women. A possible relationship between this decrease and vitamin B6 deficiency is currently under study.

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