Adjuvant Therapy of Breast Cancer
This study aims to investigate if CYP2D6 metabolizer status is associated with tamoxifen-related endocrine symptoms, tamoxifen discontinuation, and
Note that ethnic differences exist in CYP2D6 activity
This study aims to analyse the effect of an early increase in tamoxifen dose in poor metabolisers (PM) on survival
As compared with poor metabolizers, ultrarapid CYP2D6 metabolizers were more likely to discontinue tamoxifen therapy (Figure 3)
CYP2C9, CYP2C19, and CYP3A5 are also involved in tamoxifen metabolism, but the impact of their genotype on the pharmacokinetics (PK) CYP2D6 AS was translated into patient’s phenotype status as poor metabolizer, PM (AS = 0), intermediate metabolizer, IM (AS = 0
Interestingly, there was no statistical difference in endoxifen levels between PMs carrying two non-functional alleles and patients with the two decreased activity alleles *41/*41 or the combination *41 /non
In the late 1970s, the metabolism of debrisoquine, and separately sparteine, were both shown to be highly variable yet controlled by a single autosomal gene, which we now know to by CYP2D6 [28,29]
It is also highly expressed in areas of the central nervous system, including the substantia nigra
The selective estrogen receptor modulator tamoxifen has been used for more than three decades to treat metastatic and early-stage receptor-positive breast cancer and, more recently, to prevent the disease
CYP2D6 variants
37 An estimated 90% of tamoxifen is demethylated by CYP3A4 to become N‐desmethyltamoxifen and then oxidized by CYP2D6 to become an active metabolite, a poor metabolizer allele, Tamoxifen is a drug used for hormone receptor-positive breast cancers, primarily metabolised by the CYP2D6 enzyme into active metabolites such as endoxifen
, Lee K
One recent study modeled the expected amount of tamoxifen (or its metabolites) required to affect estrogen receptors, and postulated that even women with a poor metabolizer CYP2D6 genotype might be able to bind over 99
For the participants who were intermediate-to-poor or poor metabolizers, it is recommended that tamoxifen be avoided with its risk of subtherapeutic failure; however, the 40 mg dose could be used Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and men
Individuals who are CYP2D6 poor metabolizers have increased levels of venlafaxine and decreased levels of ODV –– this appears to translate into Whirl-Carrillo M, et al
Women who were identified by CYP2D6 testing as poor metabolizers of tamoxifen had a 9
CYP2D6 is a key enzyme in tamoxifen metabolism, transforming it into its main active metabolite, endoxifen