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A prognostic signature for hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer

  • 0Department of Plastic and Reconstructive Surgery, Shanghai Geriatric Medical Center, Shanghai, China.
Scientific Reports +

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July 22, 2025

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July 22, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

A new prognostic signature (HBPS) for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) predicts poor prognosis and drug resistance. This signature highlights cell cycle genes for better treatment strategies.

Area Of Science

  • Oncology
  • Genomics
  • Molecular Biology

Background

  • Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) is the most common subtype.
  • Drug resistance, especially in metastatic BC, remains a significant clinical challenge.
  • Cell cycle-related genes are implicated in cancer progression, but their role in HR+/HER2- BC drug resistance is unclear.

Purpose Of The Study

  • To develop and validate a novel prognostic signature for HR+/HER2- BC.
  • To investigate the relationship between cell cycle genes, prognosis, and drug resistance in HR+/HER2- BC.
  • To explore the biological mechanisms underlying the prognostic signature.

Main Methods

  • Development of the HR+/HER2- BC Prognostic Signature (HBPS) using cell cycle-related gene expression and Cox analysis.
  • Utilized TCGA dataset for training (421 patients) and GEO/cBioPortal datasets for validation (3605 patients).
  • Explored biological mechanisms, immune cell infiltration, signaling pathways, and drug susceptibility associated with the HBPS score.

Main Results

  • High HBPS scores were significantly associated with worse prognosis in all patient cohorts.
  • The high HBPS score group showed reduced immune cell infiltration and downregulated KRAS and IL2-STAT5 signaling.
  • Deficiency in CDKN2C, a key gene in HBPS, correlated with an immuno-cold tumor microenvironment and increased BC cell aggressiveness.

Conclusions

  • The HBPS is a robust predictor of poor prognosis and drug resistance in HR+/HER2- BC.
  • The study provides insights into the biological mechanisms, including immune evasion and signaling pathways, associated with poor outcomes.
  • The HBPS holds potential for informing precise drug treatments and improving patient management in HR+/HER2- BC.

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