From the FDA Drug Label
Tamoxifen citrate tablets are a prescription medicine that is like estrogen (female hormone) in some ways and different in other ways. In the breast, tamoxifen citrate tablets can block estrogen’s effects. Because it does this, tamoxifen citrate tablets may block the growth of breast cancers that need estrogen to grow (cancers that are estrogen- or progesterone-receptor positive)
The mechanism of action of Tamoxifen (tamoxifen citrate) is to block estrogen's effects in the breast, which can help to inhibit the growth of breast cancers that are estrogen- or progesterone-receptor positive. 1
From the Research
Introduction to Tamoxifen Mechanism of Action
Tamoxifen, a selective estrogen receptor modulator (SERM), is widely used in the treatment and prevention of breast cancer, particularly in estrogen receptor alpha (ERα/ESR1) -positive cases [ 2 ]. Its mechanism of action involves competitively binding to ERα, leading to the recruitment of co-repressors and the inhibition of transcription of genes involved in the proliferation of breast cancer epithelium.
Mechanism of Action
The therapeutic effect of tamoxifen is primarily attributed to its ability to antagonize estrogen-dependent growth by binding estrogen receptors (ERs) and inhibiting proliferation of breast epithelial cells [ 3 ]. However, tamoxifen also exhibits estrogenic agonist effects in other tissues, such as bone and endometrium, due to liganded ER activating target genes in these cell types.
Key Aspects of Tamoxifen's Mechanism
- Binding to ERα: Tamoxifen binds to ERα, leading to the inhibition of estrogen-dependent gene transcription [ 2 ].
- Recruitment of Co-repressors: The binding of tamoxifen to ERα results in the recruitment of co-repressors, which further inhibits gene transcription [ 2 ].
- ERα-Independent Effects: Recent studies have reported ERα-independent effects of tamoxifen, which may contribute to its therapeutic efficacy [ 2 ].
Treatment and Dosage
Tamoxifen is typically administered orally, with a standard dosage of 20 mg per day [ 3 ]. The treatment duration varies depending on the specific indication, ranging from several years for adjuvant therapy to indefinite use for cancer prevention.
Differentials and Caveats
- Resistance to Tamoxifen: The development of resistance to tamoxifen is a significant concern, with various mechanisms contributing to reduced efficacy [ 4 ].
- Alternative Therapies: Other SERMs, such as raloxifene, have been developed with reduced agonist profiles and may offer improved efficacy and reduced toxicity compared to tamoxifen [ 3 ].
Conclusion
In conclusion, tamoxifen's mechanism of action involves the competitive binding to ERα, leading to the inhibition of estrogen-dependent gene transcription and the recruitment of co-repressors. While tamoxifen remains a widely used and effective treatment for breast cancer, its limitations, including the development of resistance and estrogenic agonist effects, highlight the need for continued research into alternative therapies and combination regimens [ 5 ].