Breast cancer model could usher in new generation of imaging, therapy

A trifecta of cells has been revealed to be the crux of breast cancer metastases. The discovery provides cutting-edge details that could revolutionize the development of diagnostic testing and therapeutic agents for breast cancer, officials at the Albert Einstein College of Medicine in New York announced yesterday.

The researchers included Maja Oktay, MD, PhD, an associate professor of pathology, and a cytopathologist at the affiliated Montefiore Health System. Previous studies showed how modeling blood cell lining and combining the three cell types created the optimal setting for metastatic growth. These were endothelial cells, perivascular macrophages, and cells that produce a substantial amount of the migration protein Mena. The latter also happens to be involved in epidermal growth factor response. When these three cells meet, it is here that cancer can enter into the blood vessel and spread—otherwise known as intravasation.

The current research put the hypothesis to the test in a collective cohort of 100 patients with invasive ductal carcinoma, which accounts for 80 percent of breast cancers. The human studies not only verified that this microenvironment led to advanced disease, but breast cancer cells that were able to cross the endothelial layer were found to have significantly higher MenaINV, an invasive isoform of Mena, than the total population of biopsied cells.

In an official statement, Oktay says that "the outcome for patients with metastatic breast cancer hasn't improved in the past 30 years despite the development of targeted therapies. It's critically important to learn more about the metastatic process so we can develop new ways to predict whether cancer will spread and identify new treatments."

Details of the research were published Nov. 25 in Science Signaling. In this most recent study, researchers also observed all of the areas where these microenvironments developed in 10 sites, each magnified 400 times, across 60 patients. Results were similar for all of the three main subtypes of ductal carcinoma.

The researchers are now teaming up with MetaStat, a biotech company based in Montclair, N.J., for the development of a diagnostic test that could help gauge patients’ risk for metastatic disease.

Furthermore, researchers noted that by blocking a process called paracrine and autocrine activation of colony-stimulating factor-1 receptor (CSF-1R), or suppressing MenaINV, transendothelial migration could be prevented. With further study, this information could lead to brand new targeted therapies for aggressive breast cancers.