Tamoxifen is a selective estrogen receptor modulator (SERM). It acts as an estrogen antagonist for binding to receptors on DNA in breast tissue, and as an estrogen agonist in endometrial, bone, and hepatic tissues. Tamoxifen inhibits estrogen-dependent synthesis of transforming growth factor-beta. Its antiestrogenic effects on the breast explain its efficacy as a treatment for estrogen receptor-positive breast carcinoma, and as prophylaxis for women at high risk for this disease.
Yet, women who take tamoxifen are at increased risk for endometrial carcinoma via its stimulatory effects on endometrial estrogen receptors. Other adverse effects of tamoxifen include hot flashes and thrombosis. SERMs have been shown to reduce the risk of breast cancer in women >50 years old. The benefits of tamoxifen prophylaxis exceed the risks only in those who have had a hysterectomy.
Tamoxifen is well known to cause a state of hypercoagulability and hypertriglyceridemia secondary to its estrogen receptor stimulating effects. Thus, patients with these preexisting conditions are at risk of exacerbation if started on tamoxifen. Trastuzumab is used to treat HER2-receptor positive breast cancer, and its use for prophylaxis is controversial. Finally, the risk of hematologic malignancies for patient in remission are not affected by tamoxifen use.