Fibroblasts and breast cancer risk in benign breast disease

Some types of benign breast disease can increase the risk of developing breast cancer. Today, that risk is determined mainly by examining the breast's epithelial cells, which are the cells that line the ducts and lobules.

However, we hope to advance different testing methods. The epithelial cells sit within a supportive tissue of fibroblasts and extracellular matrix. This surrounding stroma is being increasingly recognized as a powerful influence on cancer development.

Our goal is to study these fibroblasts to help identify which benign breast disease is at risk of turning into cancer.

Building on our long-standing work with myofibroblasts, we're now studying populations of cancer-predisposing fibroblasts in benign breast lesions. We're investigating whether the features and spatial organization of the fibroblasts signal future breast cancer risk.

In sclerosing adenosis, we found that biopsies from women who later developed cancer showed an immune-cold tissue field, with fewer protective immune cells positioned near the epithelium.

We're extending this approach to other benign lesions in which fibroblasts are prominent, including fibroadenoma and pseudoangiomatous stromal hyperplasia. We're using multiplex imaging, spatial profiling and measurements of how fibroblasts remodel the surrounding collagen to test whether the makeup and arrangement of these cells can indicate who will develop breast cancer.

To learn how these fibroblasts act, we're using our living tissue resource to isolate fibroblasts from benign lesions and from healthy and cancerous breast tissue. This allows us to study the cells outside of the body. In 3D cultures with breast epithelial cells and in assays that measure how fibroblasts remodel and stiffen the surrounding matrix, we're testing whether and how these cells push neighboring epithelium toward cancer.

Our aim is to turn these discoveries into a simple, fibroblast-based test that could be added to the standard examination of a breast biopsy. By reading the stroma and the epithelium, we hope to identify which types of benign breast disease pose the greatest risk, and to open new opportunities to prevent breast cancer.