Comparative Tolerability of First-Generation Selective Estrogen Receptor Modulators in Breast Cancer Treatment and Prevention

In general, the selective estrogen receptor modulators (SERMs) currently indicated for the treatment and prevention of breast cancer, i.e. tamoxifen and toremifene, are fairly well tolerated. However, tamoxifen has been shown to induce hepatocellular carcinomas in rats, but not in humans, and can increase the risk of endometrial cancer in humans by two to three times. Other potentially serious adverse effects which have been associated with tamoxifen and toremifene therapy include vasomotor symptoms, an increased risk of venous thromboembolic events, and an increased incidence of cataracts and ocular toxicity, fatty liver, and nonmalignant hepatic and uterine changes. In addition, long term tamoxifen use almost always results in resistance to the drug and, indeed, has actually been shown to promote tumour proliferation in human breast cancer cells. Both tamoxifen and toremifene display drug interactions with a variety of drug classes.