Researchers Develop Predictive Test For Breast Cancer Metastasis
Most deaths from breast cancer occur because the cancer spreads, or metastasizes, to one or more vital organs. The medical quest, therefore, has been to find the best predictor(s) of metastasis, so that appropriate intervention can occur before metastasis takes place or, at the very least, early in the process. Having determined the set of cellular circumstances that lead to the spread of breast cancer, researchers at the Einstein Cancer Center and the Montefiore Einstein Center for Cancer Care, developed a test to search for these factors.
In earlier studies, researchers observed that for metastasis to occur, three particular cells must be in direct contact on a blood vessel wall. The illustration above depicts: 1) a tumor cell that produces the protein MENA; 2) a peri-vascular macrophage (cells that guide tumor cells to blood vessels); and 3) a blood vessel endothelial cell. This trio of cells in contact with each other forms a TMEM, or "tumor microenvironment of metastasis."
According to Joan Jones, M.D., senior author of the study published in the online Journal of the National Cancer Institute (JNCI), current tests look for changes in gene expression or the protein levels associated with growth of tumors. "By contrast," Jones said, "Our test is based on what Einstein researchers learned from intravital imaging, which reveals biological processes deep within the tissues of a living animal. Using this technology, they determined how breast cancer tumor cells spread in rodents."
Jones and her pathologist team studied tumor cells from 259 women with estrogen receptor positive/HER2 disease, the most common type of breast cancer, and classified the subjects into three groups based on the number of TMEMs in their cells. The risk of 'distant metastasis' turned out to be 2.7 times higher in the group with the highest number of TMEMs than the risk in the lowest TMEM group.
For comparison, the cells were also tested with the prognostic IHC4 test that measures levels of specific proteins in breast cancer cells. Results of the IHC4 test are highly corroborative with the Oncotype DX test, which measures gene expression. But the results of the TMEMs tests conducted in the Einstein study did not show corroboration with the IHC4 test, the TMEM results being highly statistically significant and the IHC4 results borderline significant,"at best."
With this test as a strong predictor of metastasis, the TMEMs establish themselves as a target for breast cancer therapy. Additionally, as was pointed out by study co-author Joshep Sparano, M.D., associate director for clinical research at the Albert Einstein Cancer Center, "This assay could eventually reduce overtreatment of early state breast cancer, which remains a major problem despite extensive use of the prognostic assays."
More TMEM studies to come!