Pharmacogenetics of aromatase inhibitors

Aromatase inhibitors (AIs) are an important class of endocrine drugs used in the treatment of early and advanced breast cancer in postmenopausal women. A number of studies have taken candidate approaches to assess the role of variants in genes encoding enzymes important in AI metabolism, notably CYP19A1 (aromatase), in AI response. These studies have shown conflicting, but interesting, results suggesting that CYP19A1 variants may be important in both the efficacy and toxicity of AIs. A recent genome-wide association study has identified a variant, creating an estrogen response element in TCL1A, which is associated with an increased risk of the musculoskeletal side effects associated with AI use. As breast cancer incidence increases, predictive biomarkers of response to AIs will become more important to ensure the most effective use of endocrine treatments.