Clinical associations of ESR2 (estrogen receptor beta) expression across thousands of primary breast tumors

Abstract

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.

A comparative analysis of clinicopathological features and survival between pre and postmenopausal breast cancer from an Indian cohort

“…SCAN-B is the large population-based cohort of primary breast tumors. Our analysis included a cohort of 3207 primary BC patients from the SCAN-B study (GSE202203) 14 and data was downloaded from Gene expression Omnibus database (GEO) 15 . TNBC patient's data (n = 320) (as per the clinical groups mentioned in the dataset) was used for analysis.…”

Identification and validation of a novel 16-gene prognostic signature for patients with breast cancer

“…This study was in compliance with strict confidentiality guidelines and regulations regarding personal data protection, all methods were carried out in accordance with relevant guidelines and regulations. We also obtained 2913 breast cancer patients from the GEO database (GSE202203) to validate the association between gene expression, risk score and overall survival 9 .…”

“…In the current study, we aimed to develop a novel gene profile to accurately estimate disease prognosis. We first examined all genes for their association with overall survival (OS) using the gene expression and clinical data of The Cancer Genome Atlas (TCGA) dataset 7 and validated the results in the Molecular Taxonomy of BRCA International Consortium (METABRIC) 8 and GSE202203 9 datasets. We next established a 16-gene score based on a linear combination of 16 gene expression levels and 16-gene nomogram to precisely predict the overall survival (OS) of BRCA patients.…”

Tamoxifen Response at Single Cell Resolution in Estrogen Receptor-Positive Primary Human Breast Tumors

“…The signature score was defined by the median expression of the signature genes. Tumors in METABRIC dataset 55 (EGAS00000000083) or SCAN-B dataset 56,78 (GSE202203) were stratified into high/low (by 50th percentile) and high/med/low (by tertiles) groups by signature scores. The gene expression data and clinical data for METABRIC were download from cBioPortal for cancer genomics 79,80 .…”