Single-cell transcriptome sequencing revealing the microenvironment of breast fibroepithelial tumor

Giant juvenile fibroepithelial tumors of the breast are rare lesions that mainly affect adolescent girls. Their pathogenesis is poorly understood, and current management relies almost entirely on surgery, which may interfere with breast development. To clarify the biological basis of these tumors, we performed single-cell RNA sequencing.

We profiled 15,295 cells from three juvenile cases (ages 12-16) and 11,442 cells from one adult patient (age 42) using the BD Rhapsody™ platform. This dataset provided a detailed cellular atlas of fibroepithelial lesions and enabled direct comparison of tumor microenvironments between juvenile and adult cases.

Distinct molecular signatures in epithelial cells and fibroblasts: Juvenile FT epithelial cells exhibited significant enrichment of proliferation-associated pathways (e.g., PI3K-Akt signaling, p = 3.2 × 10^-5; GnRH signaling, p = 1.8 × 10^-4), whereas adult lesions were dominated by estrogen receptor pathways (p = 2.6 × 10^-6). Juvenile-specific antigen-presenting fibroblasts: Comprising 18.7 % of stromal cells (vs. <1 % in adults), these were immunohistochemically validated to express high levels of HLA-DRA and CD74. Enhanced intercellular communication networks: Juvenile lesions showed active stromal-epithelial crosstalk mediated by ligand-receptor interactions such as PTN-SDC4 (p < 0.001) and MDK-NCL (p = 0.003), suggesting a role in tumor progression.

Our findings reveal molecular features that may underlie the rapid growth of juvenile giant fibroepithelial tumors. The data point to hormone-independent proliferative programs and immune-modulating fibroblast subtypes as key contributors. These insights broaden our understanding of tumor biology and may guide the development of targeted, less invasive treatments for young patients.