The PvuII (rs2234693) Single Nucleotide Polymorphism (SNP) in the gene coding for the
estrogen receptor-1 (ESR1), has been found associated with outcome in
tamoxifen treated patients with early
hormone-receptor positive
breast cancer. However, it remains unclear whether this SNP is a predictive marker for
tamoxifen efficacy or a prognostic marker for
breast cancer outcome. The aim of this study was to examine the prognostic potential of this SNP in postmenopausal early
breast cancer patients treated with adjuvant
exemestane. Dutch postmenopausal patients randomised to 5 years of adjuvant
exemestane of whom tissue was available (N = 807) were selected from the
Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial database. The SNP rs2234693 in the ESR1 gene was genotyped on
DNA from
formalin-fixed
paraffin embedded (FFPE)
tumor tissue using Taqman assays and related to the primary endpoint disease-free survival (DFS) and secondary endpoint overall survival (OS). Survival analyses were performed using Cox regression analysis. In total 805 patients were included in the analyses (median follow up of 5.22 years) and genotypes were obtained in 97% of the samples. The variant T allele of PvuII in ESR1 (rs2234693) was associated with a better DFS (hazard ratio (HR) 0.689, 95% confidence interval (CI) 0.480-0.989, P = 0.044) in univariate analysis only, and a better OS in both univariate (HR 0.616, 95%, CI 0.411-0.923, P = 0.019) and multivariate analyses (HR 0.571, 95% CI 0.380-0.856, P = 0.007), consistent with a prognostic rather than a predictive
drug response effect. Variation of PvuII in the ESR1 gene is related to OS in postmenopausal, early HR + breast
cancer patients treated with
exemestane in the TEAM study. Variation in the ESR1 gene may therefore be a prognostic marker of early
breast cancer survival, and warrants further research.