Phyllodes Tumors and Fibroepithelial Lesions of the Breast

Phyllodes tumours are uncommon fibroepithelial neoplasms characterised by a dual composition of epithelial and mesenchymal (stromal) components. They account for less than 1% of all breast tumours and are classified histologically as benign, borderline or malignant based on stromal cellularity, atypia, mitotic activity and tumour margins. Fibroepithelial lesions encompass a spectrum from the ubiquitous fibroadenoma to the rarer phyllodes tumour, sharing early molecular events such as MED12 mutations but diverging in later genetic alterations, including TERT promoter hotspots in higher-grade phyllodes. Clinically, phyllodes tumours often present as rapidly enlarging palpable masses, with imaging features overlapping those of fibroadenomas, leading to diagnostic challenges. Wide local excision with clear margins remains the mainstay of management, and research into the cellular heterogeneity, recurrence predictors and targeted therapies is driving a more nuanced understanding of these lesions at single-cell, molecular and morphological levels.

Research from Nature Portfolio

Recent studies have employed single-cell RNA sequencing and patient-derived organoid systems to map the cellular architecture of fibroadenomas, a key fibroepithelial model. These analyses revealed distinct epithelial subpopulations exhibiting concurrent hormone-sensitive and hormone-resistant signalling through ERBB2, BCL2 and CCND1 pathways. Functional assays in expandable organoids demonstrated that while many are resistant to tamoxifen monotherapy, combining tamoxifen with targeted inhibitors against ERBB2, BCL2 or CCND1 markedly reduced organoid viability. This work highlights a precision-medicine approach to counteract endocrine resistance in fibroepithelial lesions.

Phyllodes Tumors and Fibroepithelial Lesions of the Breast publication trend

The graph below shows the total number of articles in phyllodes tumors and fibroepithelial lesions of the breast across all publications each year (not limited to Nature Index journals).

Technical terms

Fibroepithelial lesion: Biphasic breast tumour comprising an epithelial component interlaced with a proliferative stromal compartment.

Phyllodes tumour: Rare fibroepithelial neoplasm of the breast classified as benign, borderline or malignant according to stromal morphology and mitotic index.

Single-cell RNA sequencing: High-resolution technique that profiles transcriptomes of individual cells to unravel intratumoural heterogeneity.

Organoid: Three-dimensional in vitro culture system derived from patient tissue that faithfully reproduces aspects of tumour architecture and function.

COL4A1/2: Type IV collagen chains central to basement membrane structure, implicated in the spatial organisation of stromal differentiation in phyllodes tumours.

References

1. Phyllodes Tumors of the Breast: A Literature Review. Cureus (2020).
2. Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets. Nature Communications (2023).
3. Integrating single‐cell and spatial transcriptomes reveals COL4A1/2 facilitates the spatial organisation of stromal cells differentiation in breast phyllodes tumours. Clinical and Translational Medicine (2024).
4. Clinical values of nuclear morphometric analysis in fibroepithelial lesions. Breast Cancer Research (2024).
5. Massively parallel sequencing analysis of synchronous fibroepithelial lesions supports the concept of progression from fibroadenoma to phyllodes tumor. npj Breast Cancer (2016).
6. MED12, TERT promoter and RBM15 mutations in primary and recurrent phyllodes tumours. British Journal of Cancer (2018).