Gene expression, molecular class changes, and pathway analysis after neoadjuvant systemic therapy for breast cancer

Area of Science:

• Genomics
• Molecular Biology
• Oncology

Background:

• Neoadjuvant systemic therapy (NST) is a common treatment for breast cancer.
• Understanding molecular changes after NST is crucial for optimizing treatment strategies.
• Residual cancer after NST presents a challenge for patient outcomes.

Purpose of the Study:

• To investigate gene expression alterations in breast cancer specimens before and after neoadjuvant systemic therapy (NST).
• To identify biological changes that could inform novel therapeutic approaches for residual disease.

Main Methods:

• Gene expression profiling of pre- and post-neoadjuvant systemic therapy (NST) breast cancer samples from 21 patients.
• Removal of stroma-associated genes to reduce confounding factors.
• Utilized PAM50 for molecular classification and paired t-tests/gene set analysis for differential expression.

Main Results:

• ER and HER2 expression remained stable; proliferation metrics showed no significant changes.
• Molecular class shifted in 33.3% of cases, often to a normal-like subtype associated with low cellularity.
• Upregulation of phosphoinositide 3-kinase, small G proteins, calmodulin-dependent protein kinase II, and energy metabolism pathways observed in basal-like cancers.
• Enrichment of notch signaling and energy metabolism, with depletion of sonic hedgehog and immune pathways in non-basal-like cancers.
• No increase in epithelial-mesenchymal transition or cancer stem cell signatures.

Conclusions:

• Residual breast cancers exhibit upregulated energy metabolism and depleted immune-related signals.
• Targeting these identified biological processes may offer promising adjuvant treatment strategies for residual disease.