biostudies-literaturede Vries Schultink AHGenentechGlaxoSmithKlineNational Cancer InstituteNCI NIH HHSA Sister&apos;s HopeNovartis567-574https://www.ebi.ac.uk/biostudies/studies/S-EPMC5812686biostudies-literatureUnknown161(3)<h4>Purpose</h4>Endoxifen concentrations have been associated with breast cancer recurrence in tamoxifen-treated patients. However, tamoxifen itself and other metabolites also show antiestrogenic anti-tumor activity. Therefore, the aim of this study was to develop a comprehensive Antiestrogenic Activity Score (AAS), which accounts for concentration and antiestrogenic activity of tamoxifen and three metabolites. An association between the AAS and recurrence-free survival was investigated and compared to a previously published threshold for endoxifen concentrations of 5.97 ng/mL.<h4>Patients and methods</h4>The antiestrogenic activities of tamoxifen, (Z)-endoxifen, (Z)-4-hydroxytamoxifen, and N-desmethyltamoxifen were determined in a cell proliferation assay. The AAS was determined by calculBreast cancer research and treatmentAn Antiestrogenic Activity Score for tamoxifen and its metabolites is associated with breast cancer outcome.PMC5812686P30 CA023100CA166293R01 CA069375R01 CA166293Huitema ADMadlensky LPierce JPAlexi Xvan Werkhoven EZwart Wde Vries Schultink AHNatarajan LLinn SCWu AHFlatt SWParker BABeijnen JHfalseAn Antiestrogenic Activity Score for tamoxifen and its metabolites is associated with breast cancer outcome.<h4>Purpose</h4>Endoxifen concentrations have been associated with breast cancer recurrence in tamoxifen-treated patients. However, tamoxifen itself and other metabolites also show antiestrogenic anti-tumor activity. Therefore, the aim of this study was to develop a comprehensive Antiestrogenic Activity Score (AAS), which accounts for concentration and antiestrogenic activity of tamoxifen and three metabolites. An association between the AAS and recurrence-free survival was investigated and compared to a previously published threshold for endoxifen concentrations of 5.97 ng/mL.<h4>Patients and methods</h4>The antiestrogenic activities of tamoxifen, (Z)-endoxifen, (Z)-4-hydroxytamoxifen, and N-desmethyltamoxifen were determined in a cell proliferation assay. The AAS was determined by calcul2017-01-01T00:00:00Z2017 Feb2025-04-04T23:17:21.508Z2019-03-26T23:02:17ZS-EPMC58126862800524610.1007/s10549-016-4083-6