Pharmacogenomic predictors of anthracycline-induced cardiotoxicity in breast cancer patients: a systematic review and meta-analysis

BACKGROUND: Anthracyclines significantly improve overall survival and play a vital role in the treatment of breast cancer. However, they are associated with cardiac dysfunction, which is often irreversible. Although anthracycline-induced cardiotoxicity (AIC) is dose-dependent, the difference in susceptibility patterns suggests the role of pharmacogenomics. Several studies explored the role of genetic variants in AIC. Integrating pharmacogenomic testing with routine anthracycline surveillance will help to predict the individuals who are at risk of developing AIC. Therefore, this current systematic review aims to evaluate and synthesize the evidence on the pharmacogenomics association of cardiotoxicity in individuals receiving anthracyclines for breast cancer treatment. METHODS: PubMed, Embase, and Scopus databases are systematically searched for the literature. After the initial search, 842 records have been identified. Following screening, 18 studies investigating genetic associations with AIC in breast cancer patients were found to be eligible for inclusion in the study. The quality of studies is assessed with the Q-Genie tool. The data is extracted and summarized with odds ratios and corresponding confidence intervals were reported. RESULTS: A total of 18 candidate gene association studies involving 4,703 breast cancer patients were included in the qualitative synthesis. Out of 57 genetic variants reported, 18 genetic variants (31.5%) are associated with an increased risk, while 3 genetic variants (5.3%) have demonstrated a risk-reducing tendency. DISCUSSION: Characterizing genetic variants in biological pathways of anthracyclines could inform precision therapy and the development of targeted interventions. The limitations of the synthesized evidence include the inadequate sample size, methodological bias within the included studies, inconsistent findings from different studies, and imprecise effect estimates. CONCLUSION: The genetic variants influence susceptibility to AIC in breast cancer patients. Further large-scale studies with longer follow-up are warranted to validate these associations and facilitate their translation into clinical practice.