P1-12-12: Evaluation of Ile655Val HER2 Polymorphism Associated with Cardiac Toxicity Following the Administration of Trastuzumab in Women with Non-Metastatic Breast Cancer.

Abstract

Abstract Background: Trastuzumab is well tolerated without major side effects except for cardiac toxicity. Although a number of clinical parameters have been associated with trastuzumab-associated cardiac toxicity (TACT), there is some indication that genetic variation of the HER2 gene may be associated with TACT in a population of metastatic breast cancer patients. However, this finding needs confirmation and we looked at a population of non-metastatic breast cancer. Purpose: This study aimed to evaluate the association between cardiac toxicity and HER2 [Ile655Val] polymorphism in non-metastatic breast cancer patients treated with trastuzumab. Method: The Ile655Val HER2 polymorphism was assessed in 41 women using TaqMan technology. For this study, the genotyping was performed using DNA extracted from normal breast tissue located at more than 1 cm of any other lesions. Charts review was used to collect information on TACT which was defined as a decrease in the left ventricular ejection fraction (LVEF) of ≥15% or ≥10% with a resulting LVEF < 50% or any follow-up LVEF of < 45%. The Fisher exact test was used to evaluate the association between cardiac toxicity and HER2 polymorphism. Results: No deviation from the Hardy-Weinberg equilibrium has been observed for the allele and genotype frequencies. The distribution of HER2 polymorphism was 10 Ile/Val (24%) and 31 Ile/Ile (76%). In this population, 22% (9/41) developed a cardiac toxicity. The Val655Ile genotype was associated with cardiac toxicity (0.03). In this preliminary study, 50% (5/10) of Ile/Val carriers compared to 13% (4/31) of Ile/Ile carriers showed TACT. Conclusion: HER2 Ile655Val polymorphism may be an efficient marker of TACT considering this tendency with this small cohort of patients. Larger sample is needed to strengthen this conclusion, since this result may influence on prescribing decision for adjuvant chemotherapy and anti-HER2 therapy in HER2 positive patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-12.