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.