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Introduction <p>Early lymph node (LN) metastasis often precedes systemic metastasis and corresponds with significantly inferior survival for patients diagnosed with early-stage breast cancer (EBC). To understand the biological pathways involved in early LN metastasis, differential gene expression (DGE) analysis compared large tumors without evidence of LN metastasis (pT2-3pN0) to small tumors with LN metastasis (pT1pN+).</p> Methods <p>This study included 2,349 patients with EBC who underwent MammaPrint and BluePrint testing as part of the FLEX (NCT03053193). DGE was performed between pT2-3pN0/pT1pN + and across their MP/BP subtypes. Immune deconvolution was assessed using gene-signature-based methods, complemented by conventional tumor-infiltrating lymphocyte (TIL) analyses on a representative subset of patients.</p> Results <p>Greater DGE was observed within the MammaPrint High Risk and BluePrint Luminal B subgroups compared to pathological stages. MammaPrint High Risk tumors saw 73 differentially expressed genes (DEGs), while 34 were found for Luminal B tumors. Gene set enrichment analysis (GSEA) of MammaPrint High Risk/Luminal B tumors showed upregulated proliferation pathways and downregulated epithelial-to-mesenchymal transition (EMT) and immune profiles in pT2-3pN0 vs. pT1pN+, respectively. Immune deconvolution analyses showed a higher abundance of T gamma delta cells and CD4 + Th1 cells and a lower abundance of T regulatory cells, M2 macrophages, and cancer-associated fibroblasts within pT2-3pN0 tumors. Conventional histological assessment revealed no significant differences in TILs.</p> Conclusion <p>This study lays the groundwork for exploring mechanisms of LN metastasis in EBC and their relation to MammaPrint High Risk and Luminal B subtypes. These data support previous studies’ association of LN metastasis with EMT and immune dysregulation.</p>

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Whole transcriptome analysis reveals MammaPrint and BluePrint-associated gene expression patterns with early lymph node metastasis in early-stage breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月8日

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  • Faisal Fa’ak,
  • Josien Haan,
  • Nicole Chmielewski-Stivers,
  • Andrea Menicucci,
  • William Audeh,
  • Phyu Phyu Soe,
  • Zhanna Logman,
  • Soojin Ahn,
  • Nina D’Abreo,
  • Jordan Baum,
  • Douglas K. Marks

摘要

Introduction

Early lymph node (LN) metastasis often precedes systemic metastasis and corresponds with significantly inferior survival for patients diagnosed with early-stage breast cancer (EBC). To understand the biological pathways involved in early LN metastasis, differential gene expression (DGE) analysis compared large tumors without evidence of LN metastasis (pT2-3pN0) to small tumors with LN metastasis (pT1pN+).

Methods

This study included 2,349 patients with EBC who underwent MammaPrint and BluePrint testing as part of the FLEX (NCT03053193). DGE was performed between pT2-3pN0/pT1pN + and across their MP/BP subtypes. Immune deconvolution was assessed using gene-signature-based methods, complemented by conventional tumor-infiltrating lymphocyte (TIL) analyses on a representative subset of patients.

Results

Greater DGE was observed within the MammaPrint High Risk and BluePrint Luminal B subgroups compared to pathological stages. MammaPrint High Risk tumors saw 73 differentially expressed genes (DEGs), while 34 were found for Luminal B tumors. Gene set enrichment analysis (GSEA) of MammaPrint High Risk/Luminal B tumors showed upregulated proliferation pathways and downregulated epithelial-to-mesenchymal transition (EMT) and immune profiles in pT2-3pN0 vs. pT1pN+, respectively. Immune deconvolution analyses showed a higher abundance of T gamma delta cells and CD4 + Th1 cells and a lower abundance of T regulatory cells, M2 macrophages, and cancer-associated fibroblasts within pT2-3pN0 tumors. Conventional histological assessment revealed no significant differences in TILs.

Conclusion

This study lays the groundwork for exploring mechanisms of LN metastasis in EBC and their relation to MammaPrint High Risk and Luminal B subtypes. These data support previous studies’ association of LN metastasis with EMT and immune dysregulation.