Adverse events associated with aromatase inhibitors: An Analysis of Real-World Datasets and drug-gene interaction network

Abstract

ABSTRACT Background Aromatase inhibitors (AIs) are commonly used to treat postmenopausal hormone receptor positive breast cancer, but there is currently a lack of comprehensive safety reports on AIs in large-scale cohorts. Research design and methods We conducted a retrospective pharmacovigilance survey based on the FDA Adverse Event Reporting System, retrieving relevant reports from the first quarter of 2004 to the third quarter of 2023, aiming to conduct a comprehensive comparative analysis of adverse reactions associated with commonly used AIs in clinical practice. Adverse event signals were assessed using disproportionality analysis. In addition, we elucidated the potential toxicological mechanisms of aromatase inhibitor related adverse events through functional enrichment analysis of human genes that interact with AIs. Results A total of 7,933 adverse event reports related to AIs were collected, and there were 642 positive signals at the preferred term level. The top three signal intensities for anastrozole are: antiphospholipid syndrome, plantar fasciitis and autoimmune pancreatitis. The top three signal intensities for letrozole are: androgenetic alopecia and myosclerosis, pneumonic herpes virus. The top three signal intensities for exemestane are: infection reactivation, thyroxine free decreased and dilatation atrial. In terms of onset time, letrozole has the earliest onset time overall, followed by exemestane, and finally anastrozole. Conclusions Our research corroborates the typical adverse events linked to AIs while highlighting potential safety concerns in their real-world clinical application.