HER2/neu 655 polymorphism, trastuzumab‑induced cardiotoxicity, and survival in HER2‑positive breast cancer patients

Abstract

Purpose HER2 overexpression in breast cancer correlates with poor outcomes. The incorporation of Trastuzumab into the treatment regimen has notably improved patient prognoses. However, cardiotoxicity emerges in approximately 20% of patients treated with the drug. This study aims to investigate the association between the HER2 655 A > G polymorphism, Trastuzumab-induced cardiotoxicity, and patient survival. Methods The study involved 88 patients treated with Trastuzumab. Cardiotoxicity, defined as a reduction in left ventricular ejection fraction (LVEF) from baseline or the emergence of clinical signs of congestive heart failure, was identified during treatment follow-up. Genotyping of HER2 655 A > G employed TaqMan SNP technology. Results Genotype frequencies of HER2/neu 655 (53 AA, 32 AG, and 3 GG) were consistent with Hardy–Weinberg equilib- rium. No significant differences were observed in mean baseline LVEF between patients who developed cardiotoxicity and those who did not. Within these groups, neither AA nor AG genotypes showed an association with changes in mean baseline or reduced LVEF levels. Logistic regression analysis, adjusted for hormonal status and anthracycline treatment, revealed that AG genotype carriers face a significantly higher risk of cardiotoxicity compared to AA carriers (OR = 4.42; p = 0.037). No association was found between the HER2/neu 655 A > G polymorphism and disease-free or overall survival, regardless of whether the data was adjusted for stage or not. Conclusion HER2 655 A > G polymorphism is significantly linked to an increased risk of Trastuzumab-induced cardiotoxic- ity but does not correlate with variations in disease-free survival or overall survival rates.