Abstract
Abstract Background. Resistance to tamoxifen remains a major clinical challenge in the treatment of breast cancer. The aim of this study was to evaluate the influence of the intensity and the pattern of estrogen receptor α (ERα) expression and common single nucleotide polymorphisms (SNP) in the estrogen receptor 1 gene (ESR1, rs2228480:2014G>A; rs2077647:+30T>C) on disease progression in breast cancer patients who received adjuvant tamoxifen. Material and methods. Formalin-fixed paraffin-embedded tumor tissue samples were retrospectively collected from 61 patients, who had distant metastasis versus distant metastasis-free breast cancers (n = 37 versus n = 24, respectively, with a 9-year follow-up). Protein expression of ER, PR and HER2 were assessed by immunohistochemistry. Real-time polymerase chain reaction analysis was used to determine the ESR1 SNPs. Results. We found that the heterogeneous distribution of ERα was statistically significant related with a low expression level and intensity of ERα in tumor tissue samples (p=0.002 and p=0.0002, respectively). In addition, the level and intensity of ERα expression was lower in patients with distant metastasis compared to distant metastasis-free cases, but these differences were not significant (P>0.05). Nonetheless, the ESR1 2014A allele was associated with a heterogeneous distribution of ERα expression (p=0.02). We showed the higher risk of distant metastasis development for the patients carrying the ESR1 2014A mutant allele compared with women with ESR1 2014G variant (p=0.04). Conclusion. These data suggest that the expression level and intensity of ERα with ESR1 2014G>A genetic variation could be a useful molecular markers for predicting tamoxifen treatment prognosis in breast cancer patients. Citation Format: Nataliya Babyshkina, Sergey Vtorushin, Stanislav Patalyak, Tatyana Dronova, Elena Slonimskaya, Nadejda Cherdyntseva. Impact of ERα expression status and ESR1 genetic variation on progression in tamoxifen-treated breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 562. doi:10.1158/1538-7445.AM2014-562
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