title: Clinical epidemiology and pharmacology of CYP2D6 inhibition related to breast cancer outcomes.
abstract: Adjuvant tamoxifen therapy of breast cancer patients with estrogen receptor-positive tumors reduces the rate of breast cancer recurrence by approximately a half. Tamoxifen is metabolized by several polymorphic enzymes, including cytochrome P450 2D6 (CYP2D6), to more active metabolites. We have reviewed the clinical pharmacology of tamoxifen and evaluated the evidence from clinical epidemiology studies regarding the association between CYP2D6 inhibition and tamoxifen effectiveness. We conclude that the impact of CYP2D6 inhibition on tamoxifen effectiveness is likely to be null or small, at least in the populations studied so far. Understanding the effect of variations in tamoxifen metabolism on breast cancer outcomes, if any, will likely require a broader perspective, including examination of the complete metabolic pathway and subgroups of patients with other markers of potentially poor tamoxifen response.
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Alle 43–45, 8200 Aarhus C., Denmark. dc@dce.au.dk
authors.forename: Deirdre P
authors.initials: DP
authors.lastname: Cronin-Fenton
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Lash
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004791:Enzyme Inhibitors; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6