X Han1, L Diao1, Y Xu1, W Xue2, T Ouyang1, J Li1, T Wang1, Z Fan1, T Fan1, B Lin1, Y Xie3. 1. Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing. 2. Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, PR China. 3. Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing zlxyt2@bjmu.edu.cn.
Abstract
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) Ile655Val polymorphism may affect the efficacy of trastuzumab treatment of breast cancer. PATIENTS AND METHODS: HER2 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. RESULTS: At 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). CONCLUSIONS: HER2 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.
BACKGROUND:Human epidermal growth factor receptor 2 (HER2) Ile655Val polymorphism may affect the efficacy of trastuzumab treatment of breast cancer. PATIENTS AND METHODS: HER2Ile655Val 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 HER2Ile655Val polymorphism and clinical outcomes in women with HER2-negative breast cancer and with HER2-positive breast cancer who received trastuzumab or who did not. RESULTS: At a median follow-up of 44 months, HER2Ile655Val polymorphism was not significantly associated with survival either in the entire study population of 4167 patients or in 2976 HER2-negative breast cancerpatients. 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). CONCLUSIONS:HER2Ile655Val polymorphism affects the function of HER2 gene only restricted in HER2-positive breast cancers. HER2-positive breast cancerpatients with the Val variant have an aggressive phenotype, but are sensitive to trastuzumab treatment.
Authors: Tung Nguyen Thanh; Bao Song Nguyen Tran; Ai Phuong Hoang Thi; Thang Tran Binh; Thong Ba Nguyen; Tam Le Minh; Quoc Huy Nguyen Vu; Thuan Dang Cong Journal: Asian Pac J Cancer Prev Date: 2021-01-01
Authors: Marco Bruno Morelli; Chiara Bongiovanni; Silvia Da Pra; Carmen Miano; Francesca Sacchi; Mattia Lauriola; Gabriele D'Uva Journal: Front Cardiovasc Med Date: 2022-04-15
Authors: Sasha E Stanton; Maureen M Ward; Paul Christos; Rachel Sanford; Christina Lam; Marta V Cobham; Diana Donovan; Ronald J Scheff; Tessa Cigler; Anne Moore; Linda T Vahdat; Maureen E Lane; Ellen Chuang Journal: BMC Cancer Date: 2015-04-11 Impact factor: 4.430