The development of the triphenylethylene derivatives has been a major advance in the treatment of breast carcinoma, due to their low toxicity. Currently there is controversy not only about their mode of action but in three main areas of clinical practice: (A) adjuvant therapy in premenopausal and oestrogen receptor-negative cases; (B) primary therapy in the elderly; (C) the prevention of breast cancer.
The United States' National Institute of Health consensus of 1985 that adjuvant tamoxifen be confined to postmenopausal women with positive nodes and ER positive tumours has been refuted by randomised clinical trials. The evidence that ER negative tumours also respond to tamoxifen has added to laboratory evidence that tamoxifen acts other than purely by oestrogen antagonism at the ER.
The use of tamoxifen as sole treatment in primary breast cancer in the elderly is being evaluated in randomised clinical trials. Two that have been reported so far have flaws which make their contradictory conclusions difficult to assess.
Recent results from the CRC trial suggest that tamoxifen has more benefit than simply preventing cancer deaths and clarification of the effects of triphenylethylenes on bone metabolism and the cardiovascular system may strengthen the case for a trial of prophylactic tamoxifen in those at risk of developing breast carcinoma.