Ahern TP, Collin LJ, Baurley JW, et al. - Given the competition of tamoxifen and its metabolites with estrogen to occupy the estrogen receptor and the conventional dose of adjuvant tamoxifen overwhelms estrogen in this competition, reducing breast cancer recurrence risk by nearly half and since phase 1 metabolism generates active tamoxifen metabolites, and phase 2 metabolism deactivates them, researchers here sought to comprehensively evaluated the metabolism and transport pathways in a large population of premenopausal women. They performed a cohort study including 5,959 Danish nonmetastatic premenopausal breast cancer patients, in whom 938 recurrences occurred, and a case-control study including 541 recurrent cases in a cohort of Danish predominantly postmenopausal breast cancer patients. Follow up was performed for 10 years. Formalin-fixed paraffin-embedded tumor blocks were assessed for 32 variants in 15 genes involved in tamoxifen metabolism or transport. Weak evidence was gained from both studies concerning the value of phase 1 metabolism in the clinical response to adjuvant tamoxifen therapy. Hence In line with prior knowledge, this study supports the role of phase 1 metabolic capacity in clinical response to tamoxifen. However, there appeared no significant association of any individual variant with risk of recurrence in either study population.