The effect of
idoxifene, a novel anti-oestrogen with less agonist activity than
tamoxifen, was compared with that of
tamoxifen on the growth of
hormone-dependent MCF-7
breast cancer xenografts. Forty tumours were established with
oestradiol support in ovariectomized athymic mice, allowed to grow to a median volume of 420 mm3 and then continued with
oestradiol, no support,
tamoxifen or
idoxifene delivered by 1.5-cm
silastic capsule. Tumour regression occurred with both anti-oestrogens, although maximum regression was observed following
oestradiol withdrawal alone. While prolonged anti-oestrogen
therapy was associated with static growth, tumour volumes were significantly lower with
idoxifene (P=0.01). After 6 months, 0/10
idoxifene-treated tumours developed acquired resistance compared with 3/10 tumours treated with
tamoxifen. In separate experiments, 94 animals were treated initially with
oestradiol,
tamoxifen,
idoxifene or placebo following implantation with 1-mm3 pieces of either wild-type (WT) or
tamoxifen-resistant (TR) MCF-7 tumour. After 4 months, only 1/11 WT tumours became established with
idoxifene compared with 4/11 with
tamoxifen, 8/12 with
oestradiol and 0/12 with placebo. Likewise, fewer TR tumours were supported by
idoxifene (3/12) than by
tamoxifen (8/12) or oestrogen (11/12). These data indicate that, compared with
tamoxifen,
idoxifene shows reduced growth support of MCF-7 xenografts and may share only partial cross-resistance. Furthermore, the development of acquired anti-oestrogen resistance may be reduced during long-term
idoxifene therapy. The
drug's reduced agonist activity may, in part, explain these observations and indicate a preferable biochemical profile for
breast cancer treatment.