{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T06:15:11Z","timestamp":1783318511281,"version":"3.54.6"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Reports of adverse drug events (ADEs) involving aromatase inhibitors (AIs) and cyclin-dependent kinase 4\/6 (CDK4\/6) inhibitors exist, but a comprehensive assessment of their combined safety in real-world practice has not been conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) database were used to collect data from the first quarter of 2015 to the third quarter of 2025. Disproportionality analysis was performed to identify ADEs associated with combination therapy. Multivariate logistic regression was used to explore factors associated with designated serious outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 28,495 reports related to combination therapy were included in FAERS. Disproportionality analysis identified 150 ADEs. The three most frequently reported ADEs were fatigue, neutropenia, and white blood cell count decreased. Signals not mentioned in drug labels were found, like skin hypopigmentation, vertigo positional, and plicated tongue. Combination therapy showed stronger reporting signals for some ADEs, including neutropenia, anaemia, and leukopenia. Among 1,186 reports in the JADER database, we identified 25 positive signals, including neutropenia, alanine aminotransferase increased, and aspartate aminotransferase increased. Multivariate logistic regression showed that body weight was associated with the occurrence of serious outcomes and hematological toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study not only identified key signals that align with earlier clinical trials but also detected several ADEs not listed in drug labeling. Concurrently, combination therapy was associated with stronger disproportionality signals for certain specific ADEs compared with monotherapy. The findings provided clinicians crucial insights and emphasized the importance of additional research centered on causality to verify the outcomes observed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1823079","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T05:37:12Z","timestamp":1783316232000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessing the risk of adverse drug events from combining aromatase inhibitors with CDK4\/6 inhibitors using the FAERS and JADER databases"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhipeng","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Oncology, Wuhan Asia General Hospital affiliated to Wuhan University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peikai","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wuhan Asia General Hospital affiliated to Wuhan University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1002\/ijc.35278","article-title":"The Globocan 2022 Cancer estimates: data sources, methods, and a snapshot of the Cancer burden worldwide","volume":"156","author":"Filho","year":"2025","journal-title":"Int J 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