Variation in the <i>ESR-1</i> gene as a prognostic marker in early breast cancer survival.

11074 Background: Variation in the genes coding for the estrogen receptor (ESR-1), CYP2c19 and UGTB15 is associated with worse outcome in tamoxifen treated early breast cancer patients. It is unclear whether this variation is a predictive marker for tamoxifen efficay or if it is a prognostic marker for breast cancer outcome. The aim of this study was to examine if SNP’s in these genes are also associated with survival in early breast cancer patients treated with adjuvant exemestane as to explore a prognostic potential of these markers. Methods: Patients of whom tissue was available were selected from the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. DNA was isolated from tumor samples. The following 4 SNPs were genotyped using Taqman assays: rs9340799 and rs2234693 in the ESR-1 gene, rs1902023 in the UGTB15 gene and rs4244285in the CYP2c19 gene. Primary endpoint was relapse-free survival (RFS) and secondary endpoint was overall survival (OS). A Kaplan-Meier analysis was performed and Cox proportional hazards models assessed survival differences. Analyses were adjusted for age at diagnosis, tumor size, nodal status, histological grade, surgery, adjuvant radiotherapy and chemotherapy. Results: 807 patients were included in the analyses and genotypes were obtained in 84%-96% of the samples. No association was found with the primary endpoint of relapse free survival with any of the four SNPS. However, the rs2234693 variant in ESR1 was associated with worse overall survival with an odds ratio of 1,4 (P = 0.016) consistent with a prognostic rather than a predictive drug response effect. Conclusions: Variation in the ESR-1 gene is related to overall survival in early breast cancer patients. Variation in the ESR-1 gene may be used as a prognostic marker of early breast cancer survival regardless of which endocrine treatment is used.