1033 Background: The introduction of trastuzumab in the treatment scheme of the HER2 BC patients has improved the evolution of the disease. Nevertheless, some of this patients develop cardiotoxicity. We studied some of our population of HER2 positive BC patients treated with trastuzumab trying to find predictors for developing cardiotoxicity, specifically the association of the HER2 Ile655Val A˃G polymorphism with trastuzumab-induced cardiotoxicity and with survival and some biochemical and clinical features. Methods: For the study breast cancer patients were recruited from San Cecilio University Hospital in Granada (Spain) who were treated with trastuzumab. HER2 Ile655Val A˃G polimorphism was performed in 93 patients using Taqman SNP technology. We analyzed the relation of polymorphisms with disease free survival (DFS) and overall survival (OS). We also could asses 66 patients who had biochemical measurement of NTpro BNP during the treatment with trastuzumab and cardiovascular risk factors including diabetes, hypertension, smoking, hypercholesterolemia and body mass index (BMI). Cardiotoxicity was defined as a ≥ 10% decrease of the left ventricular ejection fraction (LVEF) from baseline, a LVEF below 40% or any clinical manifestation of heart insufficiency. NT-proBNP cut-off points were considered to stablish normal or abnormal values adjusted by patient age. Results: Genotype frequencies of HER2/neu 655 met Hardy-Weinberg equilibrium (p = 0.363). Logistic regression analysis adjusted by hormonal status and anthracycline treatment showed higher cardiotoxicity risk for AG vs AA Her2-Ile655 polimorphism (OR = 3.00, CI95% 1.07-8.41, p = 0.037) or for AG vs AA+GG Her2-Ile655 polimorphism (OR = 3.21, CI95% 1.15-8.96, p = 0.026). We did not find association between HER2neu Ile655Val polymorphism and DFS or OS. NT-proBNP baseline higher than the range (OR 5.9, 95% CI 1.2 - 28.5, p = 0.028) and diabetes mellitus (OR 22.0, 95% CI 5.7 - 85.4, p = 0.000) were found to be related with the development of cardiotoxicity. Conclusions: HER2-Ile655 A˃G polymorphism is significantly associated with higher risk of trastuzumab-induced cardiotoxicity but it is not correlated with DFS neither OS. Diabetes or baseline high NT-proBNP levels are predictors for the development of trastuzumab-induced cardiotoxicity. These parameters should be considered for a closer follow up and for preventive actions as accurate glycaemic control for patients who will receive trastuzumab.
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