AUTHOR=Prevost Rachel , Chretien Basile , Minoc Elise-Marie , Dolladille Charles , Da-Silva Angélique , Nehme Ahmad , Joly Florence , Lelong-Boulouard Véronique , Bastien Etienne 

TITLE=Neurocognitive impairment in females with breast cancer treated with endocrine therapy and CDK4/6 inhibitors: a pharmacovigilance study using the World Health Organization’s database

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1278682

DOI=10.3389/fphar.2023.1278682

ISSN=1663-9812

ABSTRACT=<p><bold>Importance:</bold> Endocrine therapies (ETs) and inhibitors of cyclin-dependent kinases-4/6 (iCDK4/6s) are a standard treatment in breast cancer. However, data on potential neurocognitive impacts remain inconsistent for ET and are scarce for iCDK4/6s.</p><p><bold>Objective:</bold> To evaluate whether ET and iCDK4/6s are associated with neurocognitive impairment (NCI).</p><p><bold>Methods:</bold> We used observational, real-world cases of NCI from the World Health Organization’s database VigiBase<sup>®</sup> to perform disproportionality analysis. Cases were defined as any symptom of NCI in females treated with ETs or iCDK4/6s. The study period was from the date of the first adverse event reported in VigiBase<sup>®</sup> with iCDK4/6s (1 January 2014) until the date of data extraction (16 March 2022). In our primary analysis, we calculated the reporting odds ratio (ROR) adjusted for age to identify a potential association between NCI and individual ETs in isolation or in combination with iCDK4/6s. We also performed subgroup analyses by the NCI class.</p><p><bold>Results:</bold> We identified 2.582 and 1.943 reports of NCI associated with ETs and iCDK4/6s, respectively. NCI was significantly associated with each ET [anastrozole: <italic>n</italic> = 405, aROR = 1.52 (95% CI: 1.37–1.67); letrozole: <italic>n</italic> = 741, aROR = 1.37 (95% CI: 1.27–1.47); exemestane: <italic>n</italic> = 316, aROR = 1.37 (95% CI: 1.22–1.53); tamoxifen: <italic>n</italic> = 311, aROR = 1.25 (95% CI: 1.12–1.40); and fulvestrant: <italic>n</italic> = 319, aROR = 1.19 (95% CI: 1.06–1.33)] and only with palbociclib for iCDK4/6s [<italic>n</italic> = 1,542, aROR = 1.41 (95% CI: 1.34–1.48)].</p><p><bold>Conclusion:</bold> These findings suggest that in females treated for breast cancer, all ETs may be associated with NCI. However, amongst iCDK4/6s, NCI may be specific to palbociclib. NCI most frequently involved learning and memory as well as language. Neurocognitive impact of treatments requires better consideration and management.</p>