Division of Oncology, Department of Clinical Sciences Lund, Lund University Cancer Center, Lund University, Medicon Village 404-B2, 22381, Lund, Sweden.
Lund University Cancer Center, Medicon Village, Lund, Sweden.
Sci Rep. 2022 Mar 18;12(1):4696. doi: 10.1038/s41598-022-08210-3.
Estrogen receptor alpha (ERα, encoded by ESR1) is a well-characterized transcription factor expressed in more than 75% of breast tumors and is the key biomarker to direct endocrine therapies. On the other hand, much less is known about estrogen receptor beta (ERβ, encoded by ESR2) and its importance in cancer. Previous studies had some disagreement, however most reports suggested a more favorable prognosis for patients with high ESR2 expression. To add further clarity to ESR2 in breast cancer, we interrogated a large population-based cohort of primary breast tumors (n = 3207) from the SCAN-B study. RNA-seq shows ESR2 is expressed at low levels overall with a slight inverse correlation to ESR1 expression (Spearman R = -0.18, p = 2.2e-16), and highest ESR2 expression in the basal- and normal-like PAM50 subtypes. ESR2-high tumors had favorable overall survival (p = 0.006), particularly in subgroups receiving endocrine therapy (p = 0.03) and in triple-negative breast cancer (p = 0.01). These results were generally robust in multivariable analyses accounting for patient age, tumor size, node status, and grade. Gene modules consistent with immune response were associated to ESR2-high tumors. Taken together, our results indicate that ESR2 is generally expressed at low levels in breast cancer but associated with improved overall survival and may be related to immune response modulation.
雌激素受体 alpha（ERα，由 ESR1 编码）是一种特征明确的转录因子，在超过 75%的乳腺癌肿瘤中表达，是指导内分泌治疗的关键生物标志物。另一方面，关于雌激素受体 beta（ERβ，由 ESR2 编码）及其在癌症中的重要性，人们知之甚少。尽管之前的研究存在一些分歧，但大多数报告表明，高 ESR2 表达的患者预后较好。为了进一步阐明 ERβ 在乳腺癌中的作用，我们对来自 SCAN-B 研究的 3207 例原发性乳腺癌患者的大型基于人群的队列进行了分析。RNA-seq 显示，ESR2 的总体表达水平较低，与 ESR1 的表达呈轻微负相关（Spearman R = -0.18，p = 2.2e-16），并且在基底样和正常样 PAM50 亚型中表达最高。ESR2 高表达的肿瘤具有较好的总体生存率（p = 0.006），特别是在接受内分泌治疗的亚组中（p = 0.03）和在三阴性乳腺癌中（p = 0.01）。这些结果在多变量分析中考虑患者年龄、肿瘤大小、淋巴结状态和分级后仍然稳健。与 ESR2 高表达肿瘤相关的基因模块与免疫反应一致。总之，我们的结果表明，ESR2 在乳腺癌中通常表达水平较低，但与总体生存率的提高相关，并且可能与免疫反应的调节有关。
