Adverse events associated with aromatase inhibitors: an analysis of real-world datasets and drug-gene interaction network.

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 2004 to the 2023, aiming to conduct a comprehensive comparative analysis of adverse reactions associated with AIs. In addition, we elucidated the potential toxicological mechanisms of AIs related adverse events through functional enrichment analysis.

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.