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However, polymorphisms in CYP2D6 lead to variable enzymatic capacities. We aimed to examine the impact of CYP2D6 polymorphisms on tamoxifen-derived side effects in breast cancer patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Eighty-six patients with hormone receptor\u2013positive breast cancer who received tamoxifen were classified as poor (PM), intermediate (IM), normal (NM), or ultrarapid (UM) metabolizers according to Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. All patients received 20\u00a0mg\/day tamoxifen for 5\u00a0years, except PM, who were dose-escalated (20\u00a0mg\/day for 4 months, 40\u00a0mg\/day for 4\u00a0months, 60\u00a0mg\/day for 4\u00a0months, then back to 20\u00a0mg\/day). Adverse events\u2014osteoarticular pain, hot flashes, asthenia, and uterine changes\u2014were analyzed by Kaplan\u2013Meier and Cox regression. A propensity score\u2013matched (PSM) subgroup was also examined.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Rapid metabolizers (RM: NM\u2009+\u2009UM) consistently showed fewer uterine changes compared to slow metabolizers (SM: PM\u2009+\u2009IM) in both the entire cohort (HR 0.20, p\u2009=\u20090.001) and the PSM subgroup (HR 0.07, p\u2009=\u20090.011). Excluding PM and UM, comparison of IM vs. NM showed similar differences (complete group: HR 0.20, p\u2009=\u20090.002; PSM subgroup: HR 0.23, p\u2009=\u20090.068). Other side effects (joint pain, hot flashes, asthenia) were not significantly associated with CYP2D6 phenotype.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Uterine alterations in breast cancer patients treated with tamoxifen appear linked to decreased CYP2D6 activity, although we observed no association between CYP2D6 and other toxicities. These findings suggest closer monitoring for uterine toxicity in individuals with impaired CYP2D6 metabolism.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s12094-025-03908-y","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T08:38:41Z","timestamp":1744360721000},"page":"3655-3663","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Influence of CYP2D6 polymorphisms on tamoxifen side effects in patients with breast cancer"],"prefix":"10.1007","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5867-6615","authenticated-orcid":false,"given":"Isabel","family":"Blancas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7075-1123","authenticated-orcid":false,"given":"Marina","family":"Linares-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9004-5362","authenticated-orcid":false,"given":"Carlos Jos\u00e9","family":"Rodr\u00edguez-Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7105-4060","authenticated-orcid":false,"given":"Fernando","family":"Rodr\u00edguez-Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"3908_CR1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","author":"F Bray","year":"2022","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Global cancer statistics, et al. 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Additionally, the research received approval from the Provincial Ethical Committee of Granada, ensuring adherence to ethical standards in the conduct of this research. The study was registered in the European Union Clinical Trials Register (). EudraCT Number: 2007\u2013002942-40. Date on which this record was first entered in the EudraCT database: 2007\u201309-11.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}}]}}