The results of this study demonstrate that ERβ enhances the anti-estrogenic effects of endoxifen in breast cancer cells likely through the actions of ERα/β heterodimers, and suggest that the achievement of higher endoxifen concentration may not be necessary in patients whose tumors express ERβ and that these same patients may benefit from tamoxifen therapy regardless of their CYP2D6 genotype. This evidence concerns the gene ESR1 and breast cancer.