FGFR2 expression relates to subtype-specific tumour microenvironment (TIME) during luminal breast cancer evolution

Area of Science:

• Oncology
• Immunology
• Cancer Research

Background:

• Fibroblast growth factor receptor 2 (FGFR2) is a key driver in luminal breast cancer (BCa).
• FGFR2's role in endocrine resistance is known, but its impact on the tumor immune microenvironment (TIME), especially during breast cancer progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC), is unclear.

Purpose of the Study:

• To investigate the association between FGFR2 expression and immune cell infiltration during BCa progression.
• To explore the relationship between FGFR2 and immune markers in different BCa subtypes, focusing on luminal A tumors.

Main Methods:

• Retrospective analysis of 99 BCa specimens using immunohistochemistry for FGFR2 and immune markers (CD8, CD68, CD163, FOXP3).
• Comparison of immune cell densities across disease stages (DCIS vs. IDC) and BCa subtypes.
• Statistical analysis of correlations between FGFR2 expression and immune markers.

Main Results:

• Progression from DCIS to IDC showed increased infiltration of CD8+ T cells and CD68+ macrophages.
• FGFR2 expression was positively correlated with CD8+, CD163+, and FOXP3+ cell densities, particularly in tumors with extensive DCIS components.
• These correlations were specific to luminal A tumors, with no significant associations found in non-luminal subtypes.

Conclusions:

• FGFR2 expression in luminal A BCa is linked to an immunosuppressive TIME, indicated by increased CD163+ macrophages and FOXP3+ T cells.
• FGFR2 and estrogen receptor signaling may synergize to promote immune evasion and tumor progression in luminal A BCa.
• Findings highlight subtype-specific interactions and warrant further investigation into FGFR2's role in BCa immune evasion, though limitations due to small subgroup sizes exist.