Mechanism of Action
Tamoxifen functions as a SERM by competitively binding to estrogen receptors in breast tissue, blocking estrogen's growth-promoting effects on breast cancer cells. 2, 3 This competitive antagonism at the estrogen receptor is the primary mechanism by which it exerts its antiestrogenic effects in breast tissue. 3
The drug is a nonsteroidal agent that demonstrates potent antiestrogenic properties by competing with estradiol for estrogen receptor protein binding sites in target tissues such as breast. 3
Tamoxifen exhibits tissue-selective effects—acting as an estrogen antagonist in breast tissue while functioning as an estrogen agonist in other tissues such as bone and endometrium. 1, 4 This dual agonist/antagonist profile is the defining characteristic of SERMs as a drug class. 4, 5
Clinical Context and Distinction from Other Drug Classes
Tamoxifen differs from aromatase inhibitors (such as anastrozole, letrozole, and exemestane), which achieve near-complete estrogen deprivation in postmenopausal women by blocking estrogen synthesis. 1 In contrast, tamoxifen works by receptor blockade rather than hormone suppression. 1
Tamoxifen is distinct from selective estrogen receptor down-regulators (SERDs) such as fulvestrant, which have high affinity for the estrogen receptor but lack any agonist activities. 6 SERDs cause degradation of the estrogen receptor, whereas tamoxifen as a SERM maintains mixed agonist/antagonist properties. 6, 5
The SERM classification encompasses other related compounds including raloxifene, toremifene, arzoxifene, and lasofoxifene, all of which share the characteristic tissue-selective estrogen receptor modulation. 1, 6
Metabolic Considerations
Tamoxifen requires metabolic activation via the cytochrome P450 system, particularly CYP2D6, which converts it to active metabolites including endoxifen and 4-hydroxytamoxifen. 3 This distinguishes it from drugs that are active in their parent form.
Medications that inhibit CYP2D6 (such as paroxetine and fluoxetine) can reduce endoxifen formation and potentially decrease tamoxifen efficacy. 1, 2 This pharmacokinetic interaction is clinically relevant when prescribing concomitant medications. 1