Investigators have developed an innovative three-dimensional (3D) model that allows them to visualize how breast tissue grows in its earliest stages, giving them the clearest view ever at the very beginnings of breast cancer.

This research was described in the August 1, 2011, issue of the journal Genes & Development. Results from this study and ongoing research at the University of Virginia (UVA; Charlottesville, USA) Health System could lead to the development of more effective drugs and even the advancement of personalized medications to treat breast cancer.

The new model represents a major scientific milestone--it is the first time scientists have been able to replicate effectively and accurately the early growth of human breast tissue outside of the body. “These findings have important implications for the study and understanding of breast cancer,” said Deborah Lannigan, PhD, associate professor in the UVA School of Medicine’s department of microbiology, immunology, and cancer biology. “Like never before, researchers around the world now have a means of understanding how breast cancer begins and progresses.”

Nearly 90% of breast cancers begin in the breast’s ducts, so knowing how they form is crucial to developing improved therapies. A network of breast ducts resembles a tree branch--each arm of the duct is elongated and cylindrical and consists of an outer layer of cells (basal) and an inner layer of cells (luminal). Some breast cancers arise from basal cells and some grow from luminal cells. The outer, basal layer of cells acts as a barrier that is thought to help keep early cancerous cells from escaping out of the ducts and spreading into the rest of the body.

UVA researchers employed their model to determine what mechanisms in the body control the development of breast ducts, particularly the outer basal cells. They discovered that a signal produced by the body, called epidermal growth factor (EGF), tells the ducts how many basal cells to produce. This finding is a significant step in determining how basal tumors might form, and how normal basal cells might block the metastasis of cancers.

Using the new model, UVA researchers also found that human breast tissue is much more sensitive to growth factors than that of mice. “These differences might explain why some drugs are less effective in patients than would have been predicted from animal studies,” suggested Ian Macara, PhD, professor of microbiology and a coinvestigator on the study.

The new model was developed by a unique multidisciplinary team of UVA Health System researchers, including the team of cell biologists Drs. Lannigan and Macara, along with breast surgeon David Brenin, MD, and pathologist Chris Moskaluk, MD, PhD. All combined their areas of expertise to design an innovative and better way of studying breast cancer at its earliest stages.

 

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