Genomic study leads to classification of fibroepithelial breast cancer and predicts tumor cell behavior

  • The study, led by VHIO, is the first to use gene expression to classify fibroepithelial tumors
  • Genomic discovery reveals decisively more objective insights into tumor classification and behavior, when compared with those assigned through histological findings

Barcelona, March 18, 2015. A study led by the Vall d´Hebron Institute of Oncology´s (VHIO) Translational Genomics Group has described the classification of fibroepithelial breast cancers according to their respective genomic characteristics. Due to the immense variability in both prognosis and behavior, these lesions are difficult to manage, but, the timely new insights recently reported in the journal Molecular Oncology, will facilitate an ultimately more objective classification and in so doing, help to more accurately predict the course of the disease. This is the first ever study to have characterized these tumors at genomic level as well as the first to associate these genomic data with prognosis and behavior.

Fibroepithelial breast lesions encompass a heterogeneous group of tumors, ranging from benign to highly aggressive. This breast cancer type represents up to around 15% of breast cancer cases, with the vast majority being fibroadenomas and, less frequently, phyllodes cancers. Up until now, classification has largely been established based on more or less subjective histologic criteria, whereby the pathologist analyzes the tumor under the microscope and classifies it across four broad groups. Histological classification is important since it determines the course of treatment. Unlike ´normal´ breast cancer however, it can differ enormously in these cases, from follow up and close observation, simple enucleation of the tumor, to aggressive surgical and systemic therapy. While at one end of the scale we have breast fibroadenomas that only require a small resection of the lesion, at the other extreme there are malignant phyllodes tumors of the breast that often recur and need to be treated aggressively, even with chemotherapy in certain cases. In the middle, we have atypical fibroadenomas, benign phyllodes cancers, and what are known as intermediate-grade tumors. Although overall, effective surgery is usually sufficient in curing the disease, some fibroepithelial lesions may recur and even metastasize to other distant organs.

The gene expression of a wide range of these tumors has for the first time been studied and genomic findings have revealed decisively more objective insights into tumor classification, behavior and diagnosis than previously established using histological findings. According to Maria Vidal, Collaborative Member of VHIO´s Translational Genomics Group, Medical Oncologist of VHIO´s Breast Cancer and Melanoma Group directed by Javier Cortés, and first author of the paper: “We studied the expression of 105 genes in a large series of these tumors and, for the first time, we compared their genomic profile with the classic genomic classification of breast cancer (Luminal A, Luminal B, basal-like, HER2-enriched and claudin-low). Interestingly, we observed that the majority of fibroepithelial breast lesions are identified genomically as normal breast tissues. However, there is a subgroup of fibroepithelial lesions, most of them phyllodes tumors, which we classify as basal-like or claudin-low tumors.”

These two breast cancer subtypes are rare but highly aggressive. “In our series, fibroepithelial tumors identified as basal-like or claudin-low behaved far more aggressively than lesions identified as ´normal´. This prediction of behavior was more optimal with molecular classification than with histologic classification”, she continues.

The use of genomics has allowed us to study the biological behavior of these tumors beyond their morphology. In short, explains Aleix Prat, Principal Investigator of VHIO´s Translational Genomics Group, “genomic data show us that fibroepithelial breast lesions may be classified objectively based on two major biological processes. One is the tumor’s proliferative index and the other, the expression of mesenchymal processes”. In other words, if in the case of a fibroepithelial lesion, a highly-proliferative genomic profile and elevated expression of mesenchymal genes are detected, it should be treated surgically with wider margins and would also require close monitoring.

In contrast, in the instance of a fibroepithelial lesion with a low-proliferation genomic profile and high expression of epithelial genes, monitoring or simple enucleation would be sufficient. The next step is to validate these findings in independent series and, in the future, assess the opportunity of incorporating the genomic test into routine clinical practice.


For more information please contact: Amanda Wren • Communication Manager Vall d’Hebron Institute of Oncology (VHIO) • Tel. +34 695 207 886


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