ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacoepidemiology
This article is part of the Research TopicInnovative Approaches in Pharmacovigilance: Enhancing Detection and Analysis of Adverse Drug Reactions in Clinical and Real-World SettingsView all 12 articles
Patterns of Neurologic and Psychiatric Toxicity Burden of Different Endocrine Therapeutics for Breast Cancer: A Global Pharmacovigilance Study Based on FAERS and VigiAccess
Provisionally accepted
- Peking University Shenzhen Hospital, Shenzhen, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Purpose: Breast cancer is the most common malignancy in women. Approximately 70% of hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer patients rely on endocrine therapy as their fundamental systemic treatment strategy. This study aims to comprehensively evaluate the patterns of neurotoxicity and psychotoxicity across different classes of endocrine therapy. Methods: Pharmacovigilance data related to endocrine therapy for breast cancer from the FDA Adverse Event Reporting System (FAERS) and WHO VigiAccess database were utilized. The disproportionality algorithms, including reporting odds ratio and information component, were employed in FAERS to investigate the patterns, influencing factors, and outcomes of neurological and psychiatric event burdens in selective estrogen receptor modulators (SERMs), selective estrogen receptor degraders (SERDs), and aromatase inhibitors (AIs). Sensitivity analysis was conducted using VigiAccess as a supplementary data source. Results: A total of 64,731 FAERS and 116,605 VigiAccess safety reports on endocrine therapies were analyzed. Neurotoxic and psychiatric events accounted for approximately 20% and 10% of these reports, respectively. The most common neurologic adverse events were headache, dizziness, and sensory impairment, while insomnia, depression, and anxiety were the most frequent psychiatric events. The disproportionality analysis indicated that SERMs showed several strong neurovascular safety signals, such as cerebral venous thrombosis and dural arteriovenous fistula. Both SERMs and AIs showed positive signals for depression, whereas SERDs did not. All therapies exhibited an “early failure” pattern in time-to-onset analyses (β=0.54-0.66). Conclusions: This study conducted a comprehensive pharmacovigilance assessment of neurotoxicity and psychiatric events in endocrine therapy for breast cancer. The findings indicated heterogeneous patterns of neuropsychiatric safety signals and reporting burdens across drug classes, offering new insights relevant to clinical monitoring practices.
Keywords: breast cancer, Endocrine therapy, Neurotoxicity, psychiatric disorders, Real-world
Received: 24 Oct 2025; Accepted: 02 Feb 2026.
Copyright: © 2026 Li, Yang, Zhang, Li, Wu, Peng and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yajie Liu
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.