• Ann. Oncol. · Jun 2014

    Association between the HER2 Ile655Val polymorphism and response to trastuzumab in women with operable primary breast cancer.

    • X Han, L Diao, Y Xu, W Xue, T Ouyang, J Li, T Wang, Z Fan, T Fan, B Lin, and Y Xie.
    • Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing.
    • Ann. Oncol. 2014 Jun 1; 25 (6): 1158-64.

    BackgroundHuman epidermal growth factor receptor 2 (HER2) Ile655Val polymorphism may affect the efficacy of trastuzumab treatment of breast cancer.Patients And MethodsHER2 Ile655Val polymorphism was determined in 4167 patients with primary breast cancer using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. We investigated the associations between the HER2 Ile655Val polymorphism and clinical outcomes in women with HER2-negative breast cancer and with HER2-positive breast cancer who received trastuzumab or who did not.ResultsAt a median follow-up of 44 months, HER2 Ile655Val polymorphism was not significantly associated with survival either in the entire study population of 4167 patients or in 2976 HER2-negative breast cancer patients. Among 816 HER2-positive patients who received adjuvant chemotherapy and/or endocrine therapy without trastuzumab treatment, patients with the Val/Ile or the Val/Val genotype had a significantly worse disease-free survival (DFS) and distant DFS (DDFS) than those with the Ile/Ile genotype (DFS, adjusted hazard ratio [HR] 1.5; 95% confidence interval [CI] 1.0-2.3; P = 0.037; DDFS, adjusted HR 1.9; 95% CI 1.2-2.9 P = 0.005). In contrast, among 212 HER2-positive patients who received chemotherapy in combination with trastuzumab treatment, patients with the Val/Ile or the Val/Val genotype had a significantly better DFS and DDFS than those with the Ile/Ile genotype (5-year DFS, 100% versus 83%; P = 0.008; 5-year DDFS, 100% versus 89%; P = 0.031).ConclusionsHER2 Ile655Val polymorphism affects the function of HER2 gene only restricted in HER2-positive breast cancers. HER2-positive breast cancer patients with the Val variant have an aggressive phenotype, but are sensitive to trastuzumab treatment.© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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