Distribution and molecular drivers of the 21-gene recurrence score in early breast cancer with low, intermediate, and high estrogen receptor expression - Report - MDSpire

Distribution and molecular drivers of the 21-gene recurrence score in early breast cancer with low, intermediate, and high estrogen receptor expression

  • By

  • Shuai Li

  • Jiahui Huang

  • Yifei Zhu

  • Jin Hong

  • Siji Zhu

  • Weiqi Gao

  • Ou Huang

  • Jianrong He

  • Weiguo Chen

  • Yafen Li

  • Xiaosong Chen

  • Kunwei Shen

  • Jiayi Wu

  • April 30, 2026

  • 0 min

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Clinical Report: 21-gene Recurrence Score in ER-low Breast Cancer

Overview

Revise to emphasize the clinical implications of higher RS values in ER-low patients.

Background

Estrogen receptor (ER)-low breast cancer represents a challenging subgroup within ER-positive breast cancers, sharing features with triple-negative breast cancer and exhibiting limited response to endocrine therapy. The 21-gene recurrence score assay is pivotal in managing ER-positive, HER2-negative early breast cancer, yet its utility in ER-low tumors remains uncertain. Understanding the RS distribution in this population is crucial for refining prognostic and therapeutic strategies.

Data Highlights

ER GroupMean RSRS >25 (%)
ER-low (1-9%)3972.9%
ER-intermediate (10-50%)3262.8%
ER-high (>50%)2442.5%

Key Findings

  • Mean RS values were 39, 32, and 24 for ER-low, ER-intermediate, and ER-high groups, respectively.
  • 72.9% of ER-low patients had RS >25, significantly higher than ER-high patients (42.5%).
  • Expression of key genes (ESR1, PGR, BCL2, SCUBE2) was significantly lower in ER-low tumors compared to ER-high tumors.
  • The proliferation module had a modest correlation with RS in ER-low tumors (R = 0.34, P = 0.0076).
  • Only 8.83% of RS variance in ER-low tumors was explained by the four gene modules analyzed.

Clinical Implications

The findings suggest that ER-low breast cancer patients, especially those under 50 years and with high clinical risk, may benefit from careful consideration of the 21-gene RS in treatment planning. The limited correlation between RS and gene expression modules indicates a need for further research to optimize prognostic assessments in this subgroup.

Conclusion

Highlight the necessity for further validation and exploration of treatment options.

References

  1. ASCO Post, 2012 -- 21-gene Recurrence Score Predicts Outcomes of Node-positive, ER-positive Patients after Adjuvant Chemoendocrine Therapy
  2. ASCO Post, 2012 -- Expert Point of View #2: Can Molecular Profiling Identify ER-positive Patients Destined for Relapse?
  3. ASCO Post, 2019 -- ASCO Breakthrough: Breast Cancer Gene-Expression Signature May Help Predict Recurrence Postradiotherapy
  4. College of American Pathologists -- Estrogen and Progesterone Receptor Testing Guidelines
  5. ECOG-ACRIN -- PACCT-1/TAILORx Clinical Trial Results Summary
  6. The ASCO Post — 16-Gene Assay Recurrence Score Predicts Recurrence After Surgery for Localized Renal Cell Carcinoma Related Articles
  7. Is Oncotype DX testing informative for breast cancers with low ER expression?
  8. Estrogen and Progesterone Receptor… | College of American Pathologists
  9. PACCT-1/TAILORx Clinical Trial Results Summary

Original Source(s)

Distribution and molecular drivers of the 21-gene recurrence score in early breast cancer with low, intermediate, and high estrogen receptor expression

  • by Shuai Li, Jiahui Huang, Yifei Zhu, Jin Hong, Siji Zhu, Weiqi Gao, Ou Huang, Jianrong He, Weiguo Chen, Yafen Li, Xiaosong Chen, Kunwei Shen, Jiayi Wu

  • April 30, 2026

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