Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, Leiden, 2300 RC, The Netherlands.
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
Sci Rep. 2021 Feb 5;11(1):3249. doi: 10.1038/s41598-021-82002-z.
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.
PvuII(rs2234693)单核苷酸多态性(SNP)位于雌激素受体-1(ESR1)的基因编码中，已被发现与接受他莫昔芬治疗的早期激素受体阳性乳腺癌患者的治疗结果相关。然而，目前尚不清楚该 SNP 是他莫昔芬疗效的预测标志物，还是乳腺癌预后的标志物。本研究旨在探讨该 SNP 在接受辅助依西美坦治疗的绝经后早期乳腺癌患者中的预后潜力。从 Tamoxifen Exemestane Adjuvant Multinational(TEAM)试验数据库中选择了荷兰绝经后患者随机接受 5 年辅助依西美坦治疗且组织可用的患者(N=807)。使用 Taqman 检测法对福尔马林固定石蜡包埋(FFPE)肿瘤组织中的 ESR1 基因中的 SNP rs2234693 进行基因分型，并将其与无病生存(DFS)的主要终点和总生存(OS)的次要终点相关联。使用 Cox 回归分析进行生存分析。共纳入 805 例患者进行分析(中位随访时间为 5.22 年)，97%的样本获得了基因型。ESR1(PvuII rs2234693)中的 PvuII 变异 T 等位基因仅在单变量分析中与更好的 DFS(风险比[HR]0.689，95%置信区间[CI]0.480-0.989，P=0.044)相关，在单变量分析和多变量分析中与更好的 OS 相关(HR 0.616，95%CI 0.411-0.923，P=0.019)和多变量分析(HR 0.571，95%CI 0.380-0.856，P=0.007)，与预测药物反应效应一致，提示具有预后而非预测药物反应效应。ESR1 基因中的 PvuII 变异与 TEAM 研究中接受依西美坦治疗的绝经后早期 HR+乳腺癌患者的 OS 相关。ESR1 基因的变异可能是早期乳腺癌生存的预后标志物，值得进一步研究。
