Effects of <i>CYP3A4</i> and <i>CYP2C9</i> Genotype on Systemic Anastrozole and Fulvestrant Concentrations in SWOG S0226
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".