Brooks JD, et al. - Researchers investigated the impact of genetically inferred CYP2D6 phenotype on the risk of contralateral breast cancer (CBC) in this study including 1,514 CBC cases and 2,203 unilateral breast cancer controls. Germline DNA from study participants were genotyped for seven single nucleotide polymorphisms. Women were classified as extensive, intermediate, and poor metabolizers of tamoxifen. Assignment of each woman to one of six possible diplotypes and a corresponding CYP2D6 activity score (AS) was done. A 20–55% reduced rate ratio (RR) of CBC was seen in relation to tamoxifen treatment among women with AS ≥ 1. No effect of tamoxifen on the RR of CBC was seen among women with no EM (extensive metabolizer) alleles and at least one PM (poor metabolizer) allele. Overall, the observed variability in the impact of tamoxifen treatment for a first breast cancer on risk of developing CBC could be attributed to the CYP2D6 phenotype.