title: New vs old fashioned oestradiol antagonists in mammary carcinoma: 'in vitro' and 'in vivo' pharmacological approaches.
abstract: The rationale underlying therapeutic strategies designed to inhibit the action of endogenous sex hormones in malignant breast cells is provided by the demonstration of their involvement in supporting the development and growth of breast carcinoma. The surgical removal of steroid-secreting glands, in order to reduce the level of oestrogens reaching their target tissues, has for years been substituted by the so-called endocrinotherapeutic approach, which is based on the counteraction of the steroid hormone activity by the hormonal receptor blockade with suitable antioestrogenic compounds. Over the past 25 years, the non-steroidal oestrogen antagonist tamoxifen has become the standard endocrine treatment for breast cancer. The triphenylethylene-derivative compound competes efficiently for binding to the oestrogen receptor, but the complex retains some transcriptional activity. Consequently, tamoxifen exhibits, both ' in vitro and in vivo ', a range of biological activity from full oestrogen antagonism to partial agonism. There is also evidence suggesting that the agonist activity of this compound may ultimately stimulate breast tumour growth, thus causing some treatment failures. Moreover, the use of tamoxifen is limited by the possible onset of drug-resistance in many patients. Nevertheless, widely tested tamoxifen has proved to be very helpful for the development of new compounds to be used as long-term adjuvant therapy or as preventive agents. These novel oestrogen antagonists belong to two major classes: tamoxifen analogs and new pure steroidal-like antioestrogens. The search for and development of compounds devoid of tamoxifen cross-resistance, with a safer toxicity profile as well as the lack of oestrogenic effects, provide the bases to improve the current therapeutic applications of antioestrogens.
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D002986:Clinical Trials as Topic; D004965:Estrogen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D011960:Receptors, Estrogen / Q000819:agonists / Q000037:antagonists & inhibitors; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use