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Tamoxifen pharmacogenetics and pharmacokinetics in early breast cancer
In the search of a manner in order to individualize endocrine therapy with tamoxifen, CYP2D6 genotyping and therapeutic drug monitoring based on endoxifen serum concentrations were proposed as potential manners to individualize tamoxifen efficacy. Both approaches have been an ongoing discussion and many studies have been published claiming both negative and positive associations. This thesis mainly focusses on CYP2D6 genotyping and endoxifen concentrations and their impact on clinical survival outcome in...Show moreFor more than 40 years, the selective estrogen receptor modulator tamoxifen has been the cornerstone of the endocrine therapy for hormone receptor-positive breast cancer patients. However, a wide variability in response to therapy is still observed since disease recurrence happens in nearly 30 % of breast cancer patients. Tamoxifen has a complex metabolism and it is mainly metabolized by CYP2D6 enzyme, among others, into endoxifen, the most active metabolite of tamoxifen.
In the search of a manner in order to individualize endocrine therapy with tamoxifen, CYP2D6 genotyping and therapeutic drug monitoring based on endoxifen serum concentrations were proposed as potential manners to individualize tamoxifen efficacy. Both approaches have been an ongoing discussion and many studies have been published claiming both negative and positive associations. This thesis mainly focusses on CYP2D6 genotyping and endoxifen concentrations and their impact on clinical survival outcome in early breast cancer patients treated with tamoxifen.Show less
- All authors
- Sanchez Spitman, A.B.
- Supervisor
- Guchelaar, H.J.; Gelderblom, A.J.
- Co-supervisor
- Dezentjé, V.O.
- Committee
- Porlietje, J.E.A.; Gelder, T. van; Water, B. van de; Mathijssen, A.H.J.
- Qualification
- Doctor (dr.)
- Awarding Institution
- Faculty of Medicine, Leiden University Medical Center [LUMC] , Leiden University
- Date
- 2021-02-18
- ISBN (print)
- 9789090341262