Persistent Metabolic Effects of Tamoxifen: Considerations for an Experimental Tool and Clinical Breast Cancer Treatment

The selective estrogen receptor (ER) modulator tamoxifen is frequently used in preclinical studies to induce Cre recombinase and generate conditional transgenic mice. In addition, it is often prescribed to treat ER-positive breast cancer, which is diagnosed in approximately 150 000 people each year. In mice, protocols to activate Cre-ER transgenes require tamoxifen administration by several methods, including oral gavage, IP injection, or intragastric injection, spanning a wide range of doses to achieve transgene induction. As a result, the reported metabolic effects of tamoxifen treatment are not always consistent with anecdotal reports from breast cancer patients, or with expected outcomes based on the overall metabolically protective role of estrogen. A greater awareness of tamoxifen's adverse metabolic effects is critical to designing studies with appropriate controls, especially those investigations focused on metabolic outcomes.

Automated summary

Tamoxifen, a selective estrogen receptor modulator, is commonly used in preclinical studies and treatment of ER-positive breast cancer. Activation of Cre-ER transgenes in mice requires tamoxifen administration through various methods and doses, leading to inconsistent metabolic effects compared to anecdotal reports and expected outcomes.