Breast Cancer Drug Reports Flag Liver-Related Events in FAERS Analysis

A pharmacovigilance analysis of US adverse-event reports has found that hepatobiliary side effects are reported unevenly across the endocrine therapies used to treat hormone receptor-positive breast cancer, with toremifene showing the strongest disproportionality signal among seven drugs examined.

The study, published in Frontiers in Endocrinology, drew on the FDA Adverse Event Reporting System (FAERS) from the first quarter of 2004 through the first quarter of 2026, covering tamoxifen, toremifene, anastrozole, letrozole, exemestane, fulvestrant, and elacestrant. Hepatobiliary adverse events were identified using prespecified MedDRA Preferred Terms, and the analysis was restricted to cases in which the endocrine drug was listed as the primary suspect and the patient’s indication was breast cancer.

After applying these criteria, the researchers assembled a cohort of 2,630 unique case reports. They then calculated reporting odds ratios (RORs) and information components (ICs) to detect whether particular drugs were reported more often than expected relative to the rest of the restricted FAERS reference population.

Toremifene stood out with the largest estimate, at an ROR of 5.91 (95% confidence interval 4.55 to 7.68) and an IC of 2.45 with a lower 95% bound of 1.96. Positive signals also appeared for letrozole, exemestane, and fulvestrant, while tamoxifen, anastrozole, and elacestrant did not meet the predefined criteria for a positive signal.

Sensitivity analyses tested how stable the signals were when the endpoint definitions, drug-role classifications, and clinical-context exclusions were varied. The signals for toremifene, letrozole, and exemestane held up across these checks, whereas the weaker fulvestrant signal proved more sensitive to the choice of analytical assumptions.

As a supplementary data source, the team also used VigiAccess for a non-equivalent exploratory disproportionality comparison based on aggregated adverse-event term counts. That analysis agreed with the prominent toremifene signal but produced discordant findings for tamoxifen, letrozole, and exemestane, underscoring that the two databases are not directly equivalent.

Analyses at the Preferred Term and High Level Term levels suggested exploratory differences in the distribution of reported hepatobiliary events across individual drugs and between therapy classes. Time-to-onset analyses pointed to an earlier concentration of reported onset times at the class level, but the authors note that within-class heterogeneity and incomplete timing data limited how far those observations could be interpreted.

The authors are explicit that these results are hypothesis-generating pharmacovigilance evidence rather than estimates of clinical incidence, comparative safety, or causal hepatotoxicity.

With those caveats in place, the study adds a structured map of how liver- and bile-related adverse events are reported across the endocrine therapy class in breast cancer, and the authors call for confirmation in clinical and pharmacoepidemiologic studies before any conclusions about real-world safety are drawn.

Subject of Research: Disproportionality analysis of hepatobiliary adverse-event reports for endocrine therapies in breast cancer using FAERS and VigiAccess

Article Title: Hepatobiliary adverse-event reporting patterns for endocrine therapies in breast cancer: a pharmacovigilance study based on FAERS and VigiAccess

Article References: Mao, W., Liu, Y., Liu, B., & Zhu, B. (2026). Hepatobiliary adverse-event reporting patterns for endocrine therapies in breast cancer: a pharmacovigilance study based on FAERS and VigiAccess. Frontiers in Endocrinology, 17, Article 1940744. https://doi.org/10.3389/fendo.2026.1940744

Image Credits: AI Generated

DOI: 10.3389/fendo.2026.1940744

Keywords: breast cancer, endocrine therapy, FAERS, VigiAccess, pharmacovigilance, hepatobiliary adverse events, toremifene, letrozole, exemestane, disproportionality analysis, drug safety, reporting odds ratio