Triple-negative breast cancer: molecular subtypes and new targets for therapy

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Triple-negative breast cancer (TNBC) is a heterogeneous disease, limiting current targeted therapy success.
• Chemotherapy remains the primary treatment, but molecularly targeted strategies show promise.
• Transcriptional analysis reveals distinct TNBC subtypes with varying treatment sensitivities.

Purpose of the Study:

• To review current and emerging targeted therapies for TNBC based on molecular subtypes.
• To highlight the need for patient stratification and integrated biomarkers in clinical trials.

Main Methods:

• Review of preclinical studies and ongoing phase II/III clinical trials.
• Analysis of transcriptional data to define TNBC subtypes.
• Identification of actionable molecular targets within TNBC subgroups.

Main Results:

• Specific targeted therapies show promise for TNBC subtypes: PARP inhibitors (BRCA-mutated), antiandrogens (AR-positive), FGFR inhibitors (FGFR amplifications), and gamma-secretase inhibitors (NOTCH mutations).
• Molecular subset-based treatment represents a future therapeutic algorithm.

Conclusions:

• Tailored therapeutic strategies for TNBC require patient stratification based on molecular biomarkers.
• Further well-designed clinical trials incorporating integrated biomarkers are essential to advance targeted therapy development for TNBC subgroups.