Influence of the HER2 Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients: a meta-analysis.

Background: The HER2 655 A>G genetic variant has recently been associated with trastuzumab-induced cardiotoxicity in HER2 breast cancer patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the cardiac toxicity of trastuzumab in breast cancer patients.

Methods: Our study population was composed of 78 HER2 breast cancer patients receiving trastuzumab. The HER2 655 A>G (rs1136201) genetic variant was genotyped using TaqMan allelic discrimination technology. Patients were classified on the basis of the occurrence of cardiotoxic events or the absence of cardiotoxic events during 1 year after the first infusion.

Results: The HER2 655 A>G polymorphism was significantly associated with cardiotoxicity: AG versus AA [P=0.012, odds ratio (OR)=5.12, 95% confidence interval (CI) 1.43-18.36], AG+GG versus AA (P=0.01, OR=5.72, 95% CI 1.50-21.76), AG versus AA+GG (P=0.005, OR=7.17, 95% CI 1.82-28.29). A meta-analysis combining these data with the results from previous studies confirmed this association.

Conclusion: Our results support the role of the HER2 655 A>G polymorphism as a genetic marker of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients.