Effect of HER2/neu 655 polymorphism on trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients.

Isabel Blancas Hospital Universitario San Cecilio, Granada, Spain info_outline Isabel Blancas, Celia Martín, Marta Legerén, Michel Martos, Silvia Sequero, Nuria Mut-Salud, Emma Gallardo, Jose Manuel Garrido, Fernando Rodríguez-Serrano

Authors Isabel Blancas Hospital Universitario San Cecilio, Granada, Spain info_outline Isabel Blancas, Celia Martín, Marta Legerén, Michel Martos, Silvia Sequero, Nuria Mut-Salud, Emma Gallardo, Jose Manuel Garrido, Fernando Rodríguez-Serrano Organizations Hospital Universitario San Cecilio, Granada, Spain, Facultad de Medicina, Universidad de Granada, Granada, Spain, Instituto IBIMER, Universidad de Granada, Granada, Spain, Dpto. Cirugía y sus Especialidades. Universidad de Granada, Granada, Spain, IBIMER, University of Granada, Granada, Spain Abstract Disclosures Research Funding Other Foundation Background: HER2 overexpression in breast cancer is associated with a poor outcome, high risk of metastasis and a reduced overall survival. The introduction of Trastuzumab in the treatment scheme improved the prognosis of these patients. Nevertheless, around 20% of patients develop cardiotoxicity. The purpose of this study is to analyze the association of the HER2 Ile655Val A > G polymorphism with trastuzumab-induced cardiotoxicity and with survival. Methods: The study included 93 patients recruited from San Cecilio University Hospital in Granada (Spain) who were treated intravenously with Trastuzumab. The cardiotoxicity was diagnosed during the treatment follow-up considering a decrease of the left ventricular ejection fraction (LVEF) from baseline or clinical manifestation of congestive heart failure. HER2 655 A > G was genotyping using TaqMan SNP technology. Results: Genotype frequencies of HER2/neu 655 met Hardy-Weinberg equilibrium ( p = 0.363). We did not find differences in baseline LVEF in patients who developed cardiotoxicity vs those who did not. However, in cardiotoxicity group, the symptomatic patients had a baseline LVEF significantly lower than non-symptomatic patients (57.7 vs 66.1, p < 0.028). Logistic regression analysis adjusted by hormonal status and anthracycline treatment showed significant differences between AG and AA (OR = 3.00, CI95% 1.07-8.41, P = 0.037) or AG and AA+GG (OR = 3.21, CI95% 1.15-8.96, P = 0.026). However, we did not find association between Her2/neu Ile655Val polymorphism and disease-free survival or global survival. Conclusions: HER2 655 A > G polymorphism is significantly associated with higher risk of trastuzumab-induced cardiotoxicity but is not associated to a differential survival rate.