Prognostic Capability of TNBC 3-Gene Score among Triple-Negative Breast Cancer Subtypes.

Area of Science:

• Oncology
• Genomics
• Biomarkers

Background:

• Triple-negative breast cancer (TNBC) is aggressive and heterogeneous, lacking targeted therapies.
• Existing prognostic tools for TNBC have limitations.
• A previously developed TNBC 3-gene score showed prognostic capability.

Purpose of the Study:

• To evaluate the prognostic performance of the TNBC 3-gene score across distinct TNBC molecular subtypes.
• To assess the association between the TNBC 3-gene score and tumor-infiltrating lymphocytes (TILs).

Main Methods:

• Pooled analysis of 204 TNBC patient data from public datasets (GSE25066, GSE58812, GSE16446) treated with neoadjuvant chemotherapy.
• Classification of TNBC cases into Lehman's subtypes after batch effect removal.
• Application of the TNBC 3-gene score to assess distant recurrence risk within each subtype.
• Retrospective evaluation of the score's association with TIL levels in 72 TNBC cases.

Main Results:

• The TNBC 3-gene score significantly discriminated risk in the pooled cohort (HR=2.41).
• The score demonstrated predictive capability in the immunomodulatory (HR=4.16) and mesenchymal stem-like (HR=18.76) subtypes.
• No significant predictive capability was observed in basal-like 1, basal-like 2, or mesenchymal subtypes.
• The score showed poor performance in the luminal androgen receptor subtype (p=0.765).
• A low TNBC 3-gene score was significantly associated with high TIL infiltration (p<0.001).

Conclusions:

• The TNBC 3-gene score is a valuable tool for predicting distant recurrence risk in TNBC patients.
• The score is particularly effective in the immunomodulatory and mesenchymal stem-like TNBC subtypes.
• The prognostic utility of the score is enhanced in TNBC subtypes characterized by tumor-infiltrating components, despite small subgroup sample sizes.