A prospective study on the effect of endoxifen concentration and CYP2D6 phenotypes on clinical outcome in early stage breast cancer patients receiving adjuvant tamoxifen.

523Background: It has been postulated that endoxifen levels are better predictors of tamoxifen efficacy than CYP2D6 phenotype. Although in a retrospective study an endoxifen threshold of 5.9 ng/ml for efficacy was described, confirmation based on prospective studies is lacking. The objective of the prospective CYPTAM study (NTR1509) is to associate endoxifen levels and, CYP2D6 phenotypes with clinical outcome in early stage breast cancer patients receiving tamoxifen. Methods: Breast cancer patients who were receiving adjuvant tamoxifen were included. Blood samples were used for CYP2D6 genotyping and endoxifen levels by Amplichip and high-performance liquid chromatography-tandem mass spectrometry assay, respectively. Endoxifen levels and CYP2D6 phenotypes were associated with relapse-free survival (RFS) by using Cox-regression analysis. Patients who changed to an aromatase inhibitor, were censored at the time of switch. Results: A total of 667 pre and post-menopausal patients were enrolled. No association ...