IntroductionTamoxifen (TAM) is a no

IntroductionTamoxifen (TAM) is a nonsteroidal molecule derived from triphenylethylene, belonging to the group of selective modulators of estrogen receptors (SERMs) [1]. It was ap- proved in 1977 by the Food and Drug Administration (FDA) for the treatment of advanced breast cancer, and is currently considered the main adjuvant for its treatment and prevention [2]. TAM has been shown to be metabol- ically activated in order to exert its antineoplastic effect [3, 4]. In humans, TAM is metabolized by enzymes ofcytochrome P450 (CYP), resulting in the generation of different metabolites. N-desmethyltamoxifen (N-DMT) is produced by the action of CYP3A4 and CYP3A5 isoforms. N-DMT can be in turn transformed to 4-hydroxy-N- desmethyl-tamoxifen, also called endoxifen (EDF), by the action of CYP2D6. Another important metabolite is 4- hydroxy-tamoxifen (4-OH TAM), which is generated by the action of the CYP2D6 isoforms and to a lesser extent CYP3A4, CYP2B6 and CYP2C19 [5–7].