Molecular Characteristics of Lymphocyte-predominant Triple-negative Breast Cancer

Anticancer Res. 2021 Apr;41(4):2133-2140. doi: 10.21873/anticanres.14985.

Abstract

Background/aim: Tumor-infiltrating lymphocytes (TILs) are considered a prognostic marker for triple-negative breast cancer (TNBC). Immune checkpoint inhibitor (ICI)-based treatments are more effective for tumors with PD-L1-positive TILs, suggesting crucial roles of TILs in the local tumor immunity. However, factors attracting TILs are still largely unknown. Focusing on tumor antigenicity, we examined TNBC samples to identify the characteristics of TIL-high tumors.

Patients and methods: Nine treatment-naïve TNBCs (TIL-high: five, TIL-low: four) were subjected to next-generation sequencing (NGS). Loss of heterozygosity (LOH) of PTEN was also analyzed.

Results: A variety of copy number variations were observed, and no genes differed significantly between TIL-high and -low groups. However, PTEN loss was more frequently observed in the TIL-high group: 60% compared to 25% in TIL-low tumors. NGS correlated well with LOH analysis in identifying PTEN loss. All three tumors with PTEN loss in the TIL-high group showed high PD-L1. All nine samples were microsatellite-stable.

Conclusion: Frequent PTEN loss and high expression of PD-L1 in TIL-high TNBC suggest that PTEN mutation may be a biomarker for ICIs.

Keywords: PD-L1; PTEN; Tumor-infiltrating lymphocytes; immune checkpoint inhibitor; microsatellite instability; triple-negative breast cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Biomarkers, Pharmacological / analysis
  • Biomarkers, Pharmacological / metabolism
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • DNA Copy Number Variations
  • DNA Mutational Analysis / methods
  • Gene Expression Regulation, Neoplastic
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Loss of Heterozygosity
  • Lymphocyte Count
  • Lymphocytes / metabolism
  • Lymphocytes / pathology
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Middle Aged
  • Mutation
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Transcriptome
  • Treatment Outcome
  • Triple Negative Breast Neoplasms / diagnosis*
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / metabolism

Substances

  • B7-H1 Antigen
  • Biomarkers, Pharmacological
  • Biomarkers, Tumor
  • CD274 protein, human
  • Immune Checkpoint Inhibitors
  • PTEN Phosphohydrolase
  • PTEN protein, human