Integrative Multiomic Profiling of Triple-Negative Breast Cancer for Identifying Suitable Therapies

Area of Science:

• Oncology
• Genomics
• Biomarker Discovery

Background:

• Triple-negative breast cancer (TNBC) is a heterogeneous malignancy with poor prognosis.
• Novel therapies often target specific biomarkers, but their correlations are poorly understood.

Purpose of the Study:

• To investigate the intercorrelations between various biomarkers in TNBC.
• To identify potential therapeutic targets and understand their molecular underpinnings.

Main Methods:

• Multimodal profiling of 95 TNBC cases.
• Quantification of tumor-infiltrating lymphocytes (TILs) via H&E staining.
• Assessment of retinoblastoma (RB), androgen receptor (AR), and PDL1 protein expression via IHC.
• Transcriptomic profiling (NanoString BC360) and targeted DNA sequencing.
• Evaluation of associations with overall survival.

Main Results:

• RB1 mRNA and protein levels correlated better with retinoblastoma functionality than mutational status.
• Luminal AR tumors segregated into basal-like and mesenchymal transcriptomic subtypes.
• PDL1-positive tumors exhibited similar biological characteristics.
• HER2-low TNBC did not show a distinct phenotype.
• Majority of TNBC were basal or HER2-enriched (PAM50), with HER2-enriched showing improved survival.

Conclusions:

• The study provides insights into biomarker utility for TNBC therapy selection.
• Reveals intercorrelations between genomic, transcriptomic, protein, and cellular biomarkers in TNBC.
• Establishes a data resource for further exploration of biomarker interplay in TNBC.