{"doi":"10.1002/pds.70157","title":"Drug Interactions With Tamoxifen and Treatment Effectiveness in Premenopausal Breast Cancer Patients: A Bayesian Joint Modeling Approach","abstract":"PURPOSE: Tamoxifen is guideline treatment for premenopausal women with estrogen receptor-positive (ER+) breast cancer. Therapeutic efficacy relies partly on tamoxifen biotransformation by CYP2D6, CYP2C19, and CYP3A4 enzymes. We conducted a cohort study to evaluate whether concomitant prescription of drugs that inhibit these enzymes impacted breast cancer recurrence. METHODS: We enrolled 4493 premenopausal women with stage I-III ER+ breast cancer (2002-2011) treated with tamoxifen. We defined time-varying CYP-inhibiting drug exposures as the proportion of overlapping days during the tamoxifen treatment period. We estimated associations of concomitant medication use with recurrence using: (1) Bayesian joint modeling (hazard ratio [HR] and 95% credible intervals [95% CrI]), (2) traditional Cox regression (HR and 95% confidence intervals [95% CI]). RESULTS: During tamoxifen therapy, 13% of the cohort used strong CYP2D6 inhibitors, 31% weak CYP2D6 inhibitors, 37% CYP2C19 inhibitors, and 12% CYP3A4/5 inhibitors. Bayesian joint models showed that women with ≥ 50% overlap between tamoxifen and CYP2D6 inhibitors had increased recurrence risk compared with 0% overlap (HR: 1.24, 95% CrI: 0.96, 1.58). No recurrence association was seen for CYP2C19 inhibitors (≥ 50% vs. 0%, HR = 1.0, 95% CrI: 0.69, 1.40), but traditional Cox models yielded positive associations for CYP2C19 overlap (≥ 50% vs. 0%, HR = 1.45, 95% CI: 1.07, 1.96). With Bayesian joint models, we observed no association between ≥ 50% versus 0% overlap with CYP3A4/5 inhibitors (HR: 0.84, 95% CrI: 0.32, 1.93). CONCLUSIONS: With Bayesian joint modeling, we saw a slight increase in recurrence among CYP2D6-inhibitor users, but no increase among CYP2C19- or CYP3A4-inhibitor users. Results from Cox regression models were less plausible.","journal":"Pharmacoepidemiology and Drug Safety","year":2025,"id":565956,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":528291,"name":"Deirdre Cronin‐Fenton","orcid":"0000-0001-9738-2284","position":1,"is_corresponding":false},{"id":352831,"name":"Per Damkier","orcid":"0000-0003-0591-7187","position":2,"is_corresponding":false},{"id":528290,"name":"Anders Kjærsgaard","orcid":"0000-0001-9433-6442","position":3,"is_corresponding":false},{"id":528292,"name":"Stephen Hamilton‐Dutoit","orcid":"0000-0003-2158-3885","position":4,"is_corresponding":false},{"id":312449,"name":"Bent Ejlertsen","orcid":"0000-0001-8761-714X","position":5,"is_corresponding":false},{"id":412165,"name":"Richard F. MacLehose","orcid":"0000-0003-2041-3710","position":6,"is_corresponding":false},{"id":533546,"name":"Peer Christiansen","orcid":"0000-0003-2748-9240","position":7,"is_corresponding":false},{"id":1320773,"name":"Rebecca A. Silliman","orcid":"0000-0001-9958-8403","position":8,"is_corresponding":false},{"id":387406,"name":"Timothy L. Lash","orcid":"0000-0002-5240-5195","position":9,"is_corresponding":false},{"id":528293,"name":"Thomas P. Ahern","orcid":"0000-0003-0440-8727","position":10,"is_corresponding":false},{"id":4464,"name":"Lindsay  J. Collin","orcid":"0000-0003-0170-2592","position":11,"is_corresponding":false},{"id":1127129,"name":"Kirsten M. Woolpert","orcid":"0000-0002-5536-7649","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T02:56:32.546082Z","pmid":"40364655","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}