TAMOXIFEN IN POSTMENOPAUSAL WOMEN - A SAFETY PERSPECTIVE

Tamoxifen is a synthetic antiestrogen with both agonist and antagonist properties. It is believed to act primarily through binding to estrog en receptors in breast cancer cells, acting as a competitive inhibitor of estrogen. Tamoxifen has a wide range of systemic effects, possibly acting on every estrogen target tissue in the body. Tamoxifen therapy is associated with a significant reduction in the risk of recurrence and death in postmenopausal women with early stage breast cancer. In a ddition, it has been shown to effectively suppress preclinical breast cancer, as evidenced by the decrease in second primary breast cancers in adjuvant trials. Tamoxifen is also the most widely used endocrine t herapy for women with metastatic breast cancer. Tamoxifen, acting pred ominantly as an estrogen agonist in the liver, has generally favourabl e effects on serum lipids in postmenopausal women. In addition, tamoxi fen has been shown to preserve bone mineral density and may even decre ase the risk of osteoporosis in these women. Most patients treated wit h tamoxifen have minimal adverse effects. Vasomotor symptoms are the m ost commonly reported events. Less frequently, vaginal discharge or dr yness, nausea and depression have been reported. A slight increase in thromboembolic events in postmenopausal women taking tamoxifen has bee n suggested in some adjuvant trials. Rarely, ocular toxicity and hepat otoxicity are found. The adverse effect of primary importance is the i ncreased incidence of endometrial carcinoma. Several studies indicate that almost all of the tumours are of low histological grade and stage , similar to those seen with exogenous estrogen use. The relative risk of endometrial cancer in women taking tamoxifen is about 2 to 4 times higher than for postmenopausal women not taking tamoxifen. The benefi ts of tamoxifen outweigh the risks in almost all postmenopausal women with estrogen receptor-positive early stage breast cancer and in all w omen with metastatic breast cancer. Should tamoxifen prove to be an ef fective chemopreventive agent for breast cancer, the risks and benefit s of treatment wilt have to be more carefully assessed for this settin g.