Oestrogen/growth factor cross-talk in breast carcinoma: a specific target for novel antioestrogens.

Breast cancer cells express receptors for and are sensitive to a variety of steroids, polypeptide hormones and growth factors; the blocking of and/or the interference with their biochemical pathways could represent a new approach to breast tumour therapy. Antioestrogens achieve such a goal by competing with oestradiol for binding to the oestrogen receptors through which intracellular effects of the hormone are mediated. Tamoxifen has undergone the most extensive clinical evaluations and represents the treatment of choice for the endocrine management of breast cancer. Nevertheless, it is well known that tamoxifen retains agonist activity both in vitro and in vivo. To circumvent this disadvantage, new molecules with steroid-like structure, represented by ICI 164,384 and ICI 182,780, have been synthesized. In this review, Alessandra de Cupis and Roberto Favoni review data about the cross-talk between the two major families of breast cancer growth regulator: oestrogens and growth factors, focusing on the use of nonsteroidal antioestrogens and the new generation of steroidal antioestrogens as possible specifically targeted inhibitors of breast tumour proliferation.