No abstract

No abstract

SummaryAfter more than a quarter of a million patient years experience with tamoxifen in the clinic, it is perhaps appropriate to re-examine the working hypothesis for the activity of this drug. This hypothesis states that tamoxifen is an anti-oestrogen which exerts its anti-tumour activity by competing for and binding to cytoplasmic oestrogen receptor protein in the tumour.The evidence that tamoxifen is an anti-oestrogen in animals and man is seen to vary from species to species and between target organs within a species. The balance of the evidence supports the conclusion that this drug acts as an oestrogen antagonist in man.If the activity of this drug were confined to an effect mediated by the oestrogen receptor (ER), there should be a clear correlation between the anti-tumour effect of tamoxifen and the presence of ER. The clinical and pre-clinical data are reviewed. Whilst the majority of the evidence points to an effect in advanced breast cancer mediated through the ER, there are data that show the correlation is not absolute. The data are examined and the evidence for non-receptor mediated anti-tumour activity is reviewed.We conclude that whilst the majority of the activity of tamoxifen is that of an anti-oestrogen mediated through the ER, compelling evidence exists that this may not be its only anti-tumour activity at normal clinical doses. These findings might explain tamoxifen's activity in some ER negative tumours.

A prospective, double-blind, randomized comparison of propranolol, 40 mg three times daily, and matching placebo showed propranolol to be no more effective than placebo in controlling hot flushes in a group of 25 perimenopausal women. Other menopausal symptoms, such as insomnia and palpitations, were equally unaffected. However, a very close correlation was found between the daily atmospheric temperature and the number of flushes occurring in the group.

No abstract

Serum concentrations of tamoxifen and its metabolite, N-desmethyltamoxifen (DMT) were determined in six post-menopausal patients with advanced breast cancer. Following a single 10-mg dose PO parent drug was detected in the serum, with a peak concentration of 17.5 ng/ml. Concentrations of the N-desmethyl metabolite were below the limit of detection (less than 2.5 ng/ml). After 21 days' oral therapy with 10 mg b.i.d. the serum concentration of tamoxifen had increased ten fold, while DMT was now present in comparable amounts. Two patients were further studied for a longer time period. There was little change in the serum concentration of tamoxifen, while the DMT increased two fold above its value at 21 days.

No abstract

No abstract