TAMOXIFEN AS AN ANTI-TUMOUR AGENT: OESTROGEN BINDING AS A PREDICTIVE TEST FOR TUMOUR RESPONSE

Abstract

SUMMARY Rats with growing 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinomata were biopsied and oestrogen-binding capacity was measured using a Sephadex LH-20 chromatography method. Tumours were measured with calipers and animals were treated for 3 weeks with tamoxifen (50 μg/day, s.c.). Tumour response was determined by the size (cm2) before and after therapy. An increase in tumour regression (ten tumours) was seen with increasing oestrogen-binding sites determined by Scatchard analysis (P < 0·01). Thirty tumours were used to determine oestrogen binding with a single dose of [3H]-oestradiol. The percentage tumour regression was linearly correlated with oestrogen-binding capacity (P < 0·01), although some tumours with high oestrogen-binding capacities only partially regressed in response to tamoxifen therapy. The time of the oestrous cycle when biopsy occurred was not a critical factor in determining oestrogen binding for prediction of response. Oestrogen binding was reduced during tamoxifen therapy.