A test of tumor microenvironment of metastasis (TMEM) predicted risk of distant metastasis in estrogen receptor–positive and HER2-negative breast cancer, according to a new study. The test may help in guiding treatment decisions and in preventing overtreatment.
“Tests assessing metastatic risk can help doctors identify which patients should receive aggressive therapy and which patients should be spared,” said lead and corresponding author Thomas Rohan, MD, PhD, professor and chair of Epidemiology & Population Health at Einstein and Montefiore. The study was led by researchers at the National Cancer Institute (NCI)─designated Albert Einstein Cancer Center of Albert Einstein College of Medicine of Yeshiva University and Montefiore Einstein Center for Cancer Care, in Bronx, New York. It was published in the Journal of the National Cancer Institute (2014; doi:10.1093/jnci/dju136).
To measure the effectiveness of the test, the researchers used it on about 500 breast tumor specimens that had been collected over a 20-year period. The test proved more accurate in predicting the risk of distant tumor spread than a test closely resembling the leading breast cancer prognostic indicator on the market.
According to the NCI, 232,340 American women developed breast cancer last year and 39,620 women died from the disease. Death from breast cancer is mainly due to distant metastasis, when cancer cells in the primary tumor invade blood vessels and travel via the bloodstream to form tumors elsewhere in the body.
Primary breast cancers metastasize when a specific trio of cells is present together in the same microanatomic site: an endothelial cell (a type of cell that lines the blood vessels), a perivascular macrophage (a type of immune cell found near blood vessels), and a tumor cell that produces high levels of Mena, a protein that enhances a cancer cell’s ability to spread. A site where these three cells touch is where tumor cells can enter blood vessels. That site is called a tumor microenvironment of metastasis, or TMEM.
A team of pathologists applied intravital imaging observations in living rodents to identify TMEMs in human breast biopsy specimens. The scientists developed a test that uses a triple immunostain containing antibodies to the three cell types that make up a TMEM. Several different imaging technologies were combined to reveal in great detail how cancer and other complex diseases get started and progress in the body, permitting the translation of basic-science observations into relevant clinical applications.
When the TMEM test was applied to samples from 259 women who later developed a distant metastasis, and was then compared to control samples from women who did not develop metastasis, the risk of distant metastasis was 2.7 times higher for women with tumors in the high-score TMEM group compared with women with tumors in the low-score TMEM group.