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ERβ Isoforms Have Differential Clinical Significance in Breast Cancer Subtypes and Subgroups.

Young Choi1, Hadong Kim2, Simcha Pollack3

  • 1Department of Pathology, Yale School of Medicine, 310 Cedar Street, New Haven, CT 06510, USA.

Current Issues in Molecular Biology
|June 20, 2022
PubMed
Summary

Estrogen receptor beta (ERβ) isoforms are differentially expressed in breast cancer subtypes, including ERα-negative and triple-negative breast cancer (TNBC). High ERβ2 and ERβ5 expression predicts poorer survival in these aggressive breast cancers.

Keywords:
breast cancerestrogen receptor betaoutcome assessmentprognosissurvival analysistherapeutic use

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Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Estrogen receptor beta (ERβ) is a key subtype in breast cancer (BCa), with varied expression in ERα-negative and triple-negative breast cancer (TNBC).
  • Previous studies on ERβ expression yield conflicting results due to isoform complexity, heterogeneity, and lack of standardized protocols.

Purpose of the Study:

  • To simultaneously investigate mRNA and protein expression of ERβ isoforms 1, 2, and 5 in diverse BCa subtypes.
  • To analyze associations between ERβ isoform expression, clinical characteristics, and overall survival (OS).

Main Methods:

  • Quantitative real-time PCR for ERα and ERβ mRNA expression in 138 patient samples and breast cancer cell lines.
  • Immunohistochemistry for protein expression of ERα, ERβ1, ERβ2, ERβ5, PR, HER2/neu, Ki-67, CK 5/6, and p53.

Main Results:

  • ERβ1, 2, and 5 isoforms show differential expression across BCa subtypes, including ERα-negative and TNBC.
  • ERβ isoform expression correlates with Ki-67 positivity, poor prognostic markers, and predicts poorer OS, particularly in specific subgroups.
  • High ERβ2 and ERβ5 expression in ERα-negative BCa and TNBC is a significant predictor of poor OS.

Conclusions:

  • Each ERβ isoform may have distinct roles in BCa, influencing clinical characteristics and patient outcomes.
  • ERβ isoforms show potential as prognostic and predictive markers, especially in ERα-negative and TNBC subgroups.
  • Standardization of ERβ testing is crucial for clinical application and further research in larger cohorts is warranted.