Hertz, Daniel L.Kidwell, Kelley M.Seewald, Nicholas J.Gersch, Christina L.Desta, ZeruesenayFlockhart, David A.Storniolo, Ana-MariaStearns, VeredSkaar, Todd C.Hayes, Daniel F.Henry, N. LynnRae, James M.2022-10-102022-10-102017-12Hertz DL, Kidwell KM, Seewald NJ, et al. Polymorphisms in drug-metabolizing enzymes and steady-state exemestane concentration in postmenopausal patients with breast cancer. Pharmacogenomics J. 2017;17(6):521-527. doi:10.1038/tpj.2016.60https://hdl.handle.net/1805/30279Discovery of clinical and genetic predictors of exemestane pharmacokinetics was attempted in 246 post-menopausal patients with breast cancer enrolled on a prospective clinical study. A sample was collected two hours after exemestane dosing at a 1 or 3 month study visit to measure drug concentration. The primary hypothesis was that patients carrying the low-activity CYP3A4*22 (rs35599367) SNP would have greater exemestane concentration. Additional SNPs in genes relevant to exemestane metabolism (CYP1A1/2, CYP1B1, CYP3A4, CYP4A11, AKR1C3/4, AKR7A2) were screened in secondary analyses and adjusted for clinical covariates. CYP3A4*22 was associated with a 54% increase in exemestane concentration (p<0.01). Concentration was greater in patients who reported White race, had elevated aminotransferases, renal insufficiency, lower body mass index, and had not received chemotherapy (all p<0.05), and CYP3A4*22 maintained significance after adjustment for covariates (p<0.01). These genetic and clinical predictors of exemestane concentration may be useful for treatment individualization in patients with breast cancer.en-USIUPUI Open Access PolicyPharmacogeneticCYP3A4*22ExemestanePharmacokineticArticle