Pure anti-oestrogens (ICI 164384 and ICI 182780) and breast cancer: is the attainment of complete oestrogen withdrawal worthwhile?

INTRODUCTION The last decade has seen the emergence of a new class of pharmacological agents termed pure antioestrogens (Wakeling 1991, 1993). These compounds, which were originally developed by ICI Pharmaceuticals Division in the UK, bind to the oestrogen receptor (ER) (Wilson et al. 1990, Wakeling et al. 1991). Figure 1 shows the structures of ICI 164384, the lead compound, and ICI 182780, which are 7α long chain analogues of oestradiol. Both the ER binding affinity and potency of ICI 182780 are greater than those observed for ICI 164384 due to the replacement of the amide function with a sulphoxide group and the fluorination of the terminal chain (Wakeling et al. 1991). Such differences, nevertheless, do not alter the intrinsic biological behaviour of the drugs, which are identical to other more recently developed steroidal and non-steroidal pure antioestrogens (Von Angerer et al. 1990, Day et al. 1991, Claussner et al. 1992