Pharmacogenetics of aromatase inhibitors: Present understanding and looking to the future

Clinicopathologic characteristics have traditionally played a predominant role in adjuvant therapy recommendations for women with breast cancer. Host genetic factors, which impact drug metabolism, drug transportation, and drug targets, may lead to a differential treatment-related outcome in breast cancer, but their role in treatment decision-making has only recently been recognized. Genetic polymorphisms in the CYP2D6 gene and pharmacologic inhibition of the enzyme lead to an altered tamoxifen metabolism, safety profile, and possibly reduced clinical benefit. Inter-individual response to therapy has also been observed with use of aromatase inhibitors, agents that have largely superseded tamoxifen in the treatment of post-menopausal hormone receptor-positive breast cancer. We review the available evidence regarding the impact of pharmacogenetic variation on the drug-response phenotype of the aromatase inhibitors.