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Effects of CYP3A4 and CYP2C9 genotype on systemic anastrozole and fulvestrant concentrations in SWOG S0226
- 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
- et al.
Published Web Location
https://doi.org/10.2217/pgs-2023-0097Abstract
Objective & methods: This study tested associations of genotype-predicted activity of CYP3A4, other pharmacogenes, 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*22 carriers) 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 CYP3A4 and CYP2C9 may affect concentrations of endocrine therapy and may be useful to personalize dosing and improve treatment outcomes.
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