ORIGINAL RESEARCH article
Front. Oncol.
Sec. Breast Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1655438
FGFR2 expression relates to subtype-specific tumour microenvironment (TIME) during luminal breast cancer evolution
Provisionally accepted
- Department of Pathology, Chair of Oncology, Medical University of Lodz, Łódź, Poland
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Background: Fibroblast growth factor receptor 2 (FGFR2) is an oncogenic driver in luminal breast cancer (BCa), with emerging evidence linking it to tumour immune microenvironment (TIME) modulation. While FGFR2’s role in endocrine resistance is established, its potential involvement in shaping immune infiltration—particularly in the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC)—remains underexplored. Methods: This retrospective study analysed 99 BCa specimens collected between 2004–2019. Immunohistochemistry was used to assess FGFR2 expression and immune markers (CD8, CD68, CD163, FOXP3). Clinical and pathological variables were evaluated, and immune cell densities were compared across disease stages and BCa subtypes (luminal vs. non-luminal). Correlations between FGFR2 expression and immune markers were assessed using non-parametric statistical tests. Results: Progression from DCIS to IDC was associated with increased infiltration by CD8+ T cells and CD68+ macrophages. FGFR2 expression showed differences between DCIS and IDC with an extensive DCIS component and was positively correlated with CD8+, CD163+, and FOXP3+ cell densities. The latter associations were exclusive to luminal A tumours, with no such correlations observed in non-luminal subtypes. Conclusions: FGFR2 expression in luminal A BCa correlates with markers of immunosuppressive TIME, particularly CD163+ macrophages and FOXP3+ T cells. These subtype-specific interactions suggest a synergistic role of FGFR2 and estrogen receptor signalling in immune evasion and tumour progression, warranting further mechanistic and therapeutic investigation. However, the small number of cases in certain subgroups, particularly DCIS and non-luminal tumours, limits the generalizability of these findings and warrants cautious interpretation.
Keywords: breast cancer, ductal carcinoma in situ, Invasive breast cancer, tumour immunemicroenvironment, Tumour-infiltrating lymphocytes, tumour-associated macrophages, Fibroblast growth factor receptors, FGFR2
Received: 27 Jun 2025; Accepted: 26 Aug 2025.
Copyright: © 2025 Sołek, Zielińska, Kordek, Romańska and Braun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Hanna Maria Romańska, Department of Pathology, Chair of Oncology, Medical University of Lodz, Łódź, Poland
Marcin Braun, Department of Pathology, Chair of Oncology, Medical University of Lodz, Łódź, Poland
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