Pharmacogenomics of breast cancer: highlighting CYP2D6 and tamoxifen.

Abstract

To review recent pharmacogenomics studies on breast cancer patients undergoing tamoxifen therapy, highlighting how our knowledge on cytochrome P450 2D6 (CYP2D6) can help to guide the development of adjuvant therapies for these patients. A comprehensive literature search was conducted. Articles reporting findings pertaining to the effect of CYP2D6 on the therapeutic efficacy of tamoxifen, those reporting how targeting CYP2D6 could inform tamoxifen-based therapy development, and those on the tamoxifen effects on cell lines and animal models were included in the review. With CYP2D6 being the primary enzyme for tamoxifen metabolism, single-nucleotide polymorphisms (SNPs) in this gene were one of the determinants in the rate of tamoxifen metabolism, thereby potentially having an effect on the efficacy of tamoxifen-based therapies. Our review indicates the potential effectiveness of targeting these SNPs, including those for the CYP2D6*10 allele (c. 100C > T), in modifying the level of tamoxifen metabolism. These findings suggest the importance of pharmacogenomics research in our understanding of the efficacy of adjuvant therapies. However, the involvement of multiple enzymes in tamoxifen metabolism, dietary factors, ethnic differences in gene frequencies, and patients' compliance to tamoxifen therapies in studies do present challenges in pharmacogenomics research. Pharmacogenomics could play important roles in mediating the advancement of tamoxifen-based adjuvant therapies. Research efforts should be directed towards the exploration of further SNPs of CYP2D6 that affect tamoxifen metabolism, as well as epigenetic changes in CYP2D6, enabling the design of precision medicine and confirming clinical validity in the use of pharmacogenomics for tamoxifen.