文献_Tamoxifen_CYP2D6_Genotype_Technical_ReviewL5691_1107_1.pdfVIP

Tamoxifen CYP2D6 Genotype Introduction ous beta blockers, opiates, selective serotonin reuptake in- There are more than 175,000 new cases of breast cancer in hibitors (SSRIs), anticyclic antidepressants, and tamoxifen. the United States expected in 2007.1 Two out of every three CYP2D6 is a polymorphic gene with more than 40 reported new cases are estrogen receptor-positive and are candidates allelic variants that code for enzymes with variable function for hormonal therapy.2 Tamoxifen, a potent estrogen recep- or loss of function. Because of the strong association be- tor modulator, has been widely used for the treatment and tween genotype and phenotype, CYP2D6 genotype can be prevention of estrogen receptor (ER)-positive breast cancer.3 determined (and enzyme function inferred) from the geno- When given to women with ER-positive breast cancer for type identified. Enzyme phenotype is designated using the five years after surgery, tamoxifen significantly reduces the following phenotypic designations: annual recurrence rate and reduces the breast cancer mortal- 4 • Extensive metabolizer (EM) or wild type, ity rate by one third. Tamoxifen’s pharmacologic effect is • Intermediate metabolizer (IM), mediated by its ability to compete with estrogen for estrogen • Poor metabolizer (PM), or receptors in breast tissue and to inhibit the stimulatory effect • Ultra metabolizer (UM). of estrogen on tumor growth. Tamoxifen is metabolized by a number of cytochrome