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

Dalal, Hina LU orcid ; Dahlgren, Malin LU ; Gladchuk, Sergii LU ; Brueffer, Christian LU orcid ; Gruvberger-Saal, Sofia K LU and Saal, Lao H LU orcid (2022) In Scientific Reports 12. p.1-12
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 =... (More)

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.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ESR2, ESR1, Breast Cancer, RNA sequencing, Gene Expression
in
Scientific Reports
volume
12
article number
4696
pages
1 - 12
publisher
Nature Publishing Group
external identifiers
  • scopus:85126679178
  • pmid:35304506
ISSN
2045-2322
DOI
10.1038/s41598-022-08210-3
project
Sweden Cancerome Analysis Network - Breast (SCAN-B): a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine
language
English
LU publication?
yes
additional info
© 2022. The Author(s).
id
bb72d109-0c00-4d63-8aef-750dbb538e11
date added to LUP
2022-04-28 10:53:36
date last changed
2025-03-12 19:28:36
@article{bb72d109-0c00-4d63-8aef-750dbb538e11,
  abstract     = {{<p>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.</p>}},
  author       = {{Dalal, Hina and Dahlgren, Malin and Gladchuk, Sergii and Brueffer, Christian and Gruvberger-Saal, Sofia K and Saal, Lao H}},
  issn         = {{2045-2322}},
  keywords     = {{ESR2; ESR1; Breast Cancer; RNA sequencing; Gene Expression}},
  language     = {{eng}},
  pages        = {{1--12}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Clinical associations of ESR2 (estrogen receptor beta) expression across thousands of primary breast tumors}},
  url          = {{http://dx.doi.org/10.1038/s41598-022-08210-3}},
  doi          = {{10.1038/s41598-022-08210-3}},
  volume       = {{12}},
  year         = {{2022}},
}