Profiles of neuropsychiatric toxicity associated with different endocrine therapies for breast cancer: a global pharmacovigilance study based on FAERS and VigiAccess.

PURPOSE: Breast cancer is the most common malignancy in women. 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).

CONCLUSION

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.