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

Han, Xinkun; Diao, Limei; Xu, Ye; Xue, Wen-han; Ouyang, Tao; Li, J.; Wang, T.; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao

doi:10.1093/annonc/mdu111

Cited by 42 publications

(39 citation statements)

References 21 publications

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“…Again however, no benefit was observed for OS for either of the alleles tested. This is consistent with previous findings by Han et al , 2014 [8]. We analyzed the frequency differences of the ERBB-family SNPs between the Irish, UK and Chinese populations to determine if ERBB SNPs differ greatly between the two populations (Table 2).…”

Section: Resultssupporting

confidence: 89%

“…This result is consistent with the Han et al study of 2014 [8] which found that the minor allele of HER2-I655V resulted in worse RFS of Chinese HER2-positive BC patients. Our analysis found no significant difference in allele frequency of the ERBB2-I655V SNP between the Chinese Han and UK/Irish populations, providing further support that the minor allele of ERBB2-I655V may be a negative prognostic marker of adjuvant trastuzumab response in women who suffer from HER2-positive BC.…”

Section: Discussionsupporting

confidence: 92%

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The impact of ERBB-family germline single nucleotide polymorphisms on survival response to adjuvant trastuzumab treatment in HER2-positive breast cancer

et al. 2016

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BackgroundTrastuzumab treatment for women with HER2-positive breast cancer (BC) resulted in the significant improvement of both relapse free survival (RFS) and overall survival (OS). However, many women who are classified as HER2-positive do not respond. Many studies have focused on the role of somatic mutations rather than germline polymorphisms in trastuzumab resistance.ResultsWe completed an Agena MassArray screen of 10 ERBB-family single nucleotide polymorphisms (SNPs) in 194 adjuvant trastuzumab treated HER2-positive BC patients. SNPs in EGFR genes have a significant association with RFS and OS. Patients with the minor allele of EGFR N158N had significantly worse OS (hazard ratio (HR) = 4.01, (confidence interval (CI) = 1.53– 10.69), p = 0.05) relative to those with either the heterozygous or wild-type (WT) allele. Patients with the minor allele of EGFR T903T (HR = 3.52, (CI = 1.38– 8.97), p = 0.05) had worse RFS relative to those with either the heterozygous or WT allele.Patients and methodsUsing next generation sequencing (NGS) we identified ERBB-family (EGFR, HER2, HER3 and HER4) single nucleotide polymorphisms (SNPs) that occurred in 2 or more patients of a 32 HER2-positive BC patient cohort. Agena MassArray analysis confirmed the frequency of these SNPs in 194 women with HER2-positive BC who received trastuzumab in the adjuvant setting. Using Kaplan-Meier estimates and Cox regression analysis we correlated the presence of ERBB-family SNPs with both RFS and OS.ConclusionsThe presence of germline ERBB-family SNPs may play an important role in how a patient responds to adjuvant trastuzumab, and clinical assessment of these SNPs by targeted genetic screening of patients' blood may be important to stratify patients for treatment.

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Section: Resultssupporting

confidence: 89%

Section: Discussionsupporting

confidence: 92%

The impact of ERBB-family germline single nucleotide polymorphisms on survival response to adjuvant trastuzumab treatment in HER2-positive breast cancer

et al. 2016

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“…The HER-2/neu (HER-2) located on chromosome 17 (17q12-q21.32) plays an important role in the growth of some cancer cells. HER-2 proto-oncogene encodes p185 HER-2 a transmembrane glycoprotein with tyrosine-specific kinase activity (5). Amplification and overexpression of HER-2 proto-oncogene has been frequently detected in approximately 30% of human ovarian, breast tumors and 26% of gastric cancers which is identified as a significant predictor of poor survival in these tumors (6).…”

Section: Introductionmentioning

confidence: 99%

HER-2/neu Overxpression in Esophageal Squamous Cell Carcinoma (ESCC) and Its Correlation with Patient’s Clinicopathological Features

et al. 2016

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Background: HER-2/neu overexpression has been reported in various human cancers and identified as a significant predictor of poor survival. In this study HER-2/neu overexpression and its associations with clinicopathological characteristics were evaluated in patients with esophageal squamous cell carcinoma (ESCC). Methods: This cross-sectional study was performed on 64 patients with histological diagnosis of primary ESCC who underwent surgery for curative treatment. Immunohistochemistry (IHC) was used to assess expression of HER-2/neu receptor in formalin-fixed paraffin-embedded tissue blocks.

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“…We recently reported that the HER2 Ile655Val polymorphism is significantly associated with the survival outcome of patients with HER2-positive breast cancer, indicating that patients with the Val variant exhibit breast cancer with an aggressive phenotype, but are more sensitive to trastuzumab treatment (14). In the present study, another common polymorphism (HER2 Pro1170Ala) of HER2 was investigated.…”

Section: Introductionmentioning

confidence: 82%

HER2 Pro1170Ala polymorphism is associated with decreased survival rate in HER2-negative breast cancer

Ouyang

et al. 2017

Oncology Letters

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Abstract. The Pro1170Ala polymorphism is one of the most common polymorphisms of human epidermal growth factor receptor 2 (HER2) and may affect the clinical outcome in breast cancer. Therefore, in the present study, the incidence of the HER2 Pro1170Ala polymorphism was determined in 3,305 female patients with operable primary breast cancer using a DNA-sequencing assay, and the potential association with survival was investigated. Of these 3,305 patients, 29% (955/3,305) were homozygous for the Pro/Pro genotype, 51% (1,679/3,305) were heterozygous for the Pro/Ala genotype and 20% (671/3,305) were homozygous for the Ala/Ala genotype. The frequency of this polymorphism conformed to the Hardy-Weinberg equilibrium (P=0.175). No significant association between the HER2 Pro1170Ala polymorphism and recurrence-free survival (RFS) or distant recurrence-free survival (DRFS) was identified in the entire cohort of 3,305 patients. HER2 status was available for 3,170/3,305 patients; no significant association between the HER2 Pro1170Ala polymorphism and survival was identified in HER2-positive patients (n=728). However, among the HER2-negative patients (n=2,442), those with the Pro/Ala or Ala/Ala genotype had a significantly decreased RFS [unadjusted hazard ratio (HR), 1.45; 95% confidence interval (CI), 1.03-2.04; P=0.033] and DRFS (unadjusted HR, 1.65; 95% CI, 1.11-2.44; P=0.012) compared with those with the Pro/Pro genotype. Multivariate analysis revealed that the Pro/Ala or Ala/Ala genotype was an independent unfavorable factor for DRFS (adjusted HR, 1.63; 95% CI, 1.05-2.53; P=0.029) in the subgroup of HER2-negative patients. The results of the present study suggest that patients with HER2-negative breast cancer with the HER2 Pro1170Ala polymorphism variant exhibit a decreased survival outcome.

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

Cited by 42 publications

References 21 publications

The impact of ERBB-family germline single nucleotide polymorphisms on survival response to adjuvant trastuzumab treatment in HER2-positive breast cancer

The impact of ERBB-family germline single nucleotide polymorphisms on survival response to adjuvant trastuzumab treatment in HER2-positive breast cancer

HER-2/neu Overxpression in Esophageal Squamous Cell Carcinoma (ESCC) and Its Correlation with Patient’s Clinicopathological Features

HER2 Pro1170Ala polymorphism is associated with decreased survival rate in HER2-negative breast cancer

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