Genomic Alterations in Quadruple-Negative Breast Cancer Tumors

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Triple-negative breast cancer (TNBC) lacking androgen receptor (AR) expression is defined as quadruple-negative breast cancer (QNBC).
• QNBC is associated with younger age, high Ki-67, and genomic instability, but its genomic landscape is not fully understood.
• Understanding QNBC's genomic characteristics is crucial for developing targeted therapies.

Purpose of the Study:

• To comprehensively describe the genomic characteristics of QNBC.
• To compare genomic profiles between QNBC and TNBC with AR expression (TNBC AR-100%).
• To identify potential therapeutic targets based on distinct genomic alterations.

Main Methods:

• Analysis of 54 TNBC cases, categorized as QNBC (TNBC AR-0%) or TNBC AR-100%.
• Assessment of clinical, molecular, and genomic parameters, focusing on pathogenic/likely pathogenic (P/LP) variants in homologous recombination repair (HRR) and cancer-related pathways.
• Measurement of homologous recombination deficiency (HRD) scores and copy number variants (CNVs).

Main Results:

• QNBC demonstrated a higher HRD score and increased CNVs compared to TNBC AR-100%.
• QNBC exhibited higher mutation rates in TP53 and the MYC signaling pathway.
• P/LP variants in HRR, PI3K/AKT, and RTK/RAS pathways were exclusively found in QNBC.

Conclusions:

• QNBC and TNBC AR-100% are distinct molecular and genomic entities.
• QNBC tumors display more aggressive characteristics and genomic instability.
• Genomic differences highlight potential for distinct therapeutic strategies in QNBC.