| Autor: |
Rutherford, Delaney V, Medley, Sarah, Henderson, Nicholas C, Gersch, Christina L, Vandenberg, Ted A, Albain, Kathy S, Dakhil, Shaker R, Tirumali, Nagendra R, Gralow, Julie R, Hortobagyi, Gabriel N, Pusztai, Lajos, Mehta, Rita S, Hayes, Daniel F, Kidwell, Kelley M, Henry, N Lynn, Barlow, William E, Rae, James M, Hertz, Daniel L |
| Zdroj: |
Pharmacogenomics; 20230101, Issue: Preprints |
| Abstrakt: |
Objective & methods:This study tested associations of genotype-predicted activity of CYP3A4, other pharmacogenes and SLC28A7(rs11648166) and ALPPL2(rs28845026) with systemic concentrations of the endocrine therapies anastrozole and fulvestrant in SWOG S0226 trial participants. Results:Participants in the anastrozole-only arm with low CYP3A4 activity (i.e., CYP3A4*22carriers) had higher systemic anastrozole concentrations than patients with high CYP3A4 activity (β-coefficient = 10.03; 95% CI: 1.42, 18.6; p = 0.025). In an exploratory analysis, participants with low CYP2C9 activity had lower anastrozole concentrations and higher fulvestrant concentrations than participants with high CYP2C9 activity. Conclusion:Inherited genetic variation in CYP3A4and CYP2C9may affect concentrations of endocrine therapy and may be useful to personalize dosing and improve treatment outcomes. |
| Databáze: |
Supplemental Index |
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