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No Evidence of Genotype-Treatment Interactions between Endocrine Therapies and Adverse Drug Effects in Women with Breast Cancer: Findings from the UK Biobank

Mokbel, K.; N. Weedon, M.; Moye, V.; S. Ruth, K.; Jackson, L.

2025-10-24 genetic and genomic medicine
10.1101/2025.10.23.25338679 medRxiv
Show abstract

Breast cancer is the most commonly diagnosed cancer worldwide. Earlier studies have demonstrated that breast cancer patients with particular genomic variants are more susceptible to adverse drug effects (ADEs) when they are receiving endocrine therapy. However, to establish a robust body of evidence with regard to the potential utility and predictive value of these variants, findings from these reports require replication. This study aimed to validate previously reported associations between genomic variants and medically important adverse drug effects (MIADEs) using UK Biobank (UKBB). In 2,729 female participants who had received endocrine therapy in the UKBB, this study found no statistically significant interactions between genomic variants and endocrine therapy regarding continuous or binary outcomes. Thus, findings from the UKBB dataset do not support previously documented pharmacogenomic associations of MIADEs in endocrine therapy. In light of current evidence, pharmacogenomic testing within this context should not be considered for individualised endocrine treatment recommendations in clinical practice.

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