A study combining tumor cells from patients with breast cancer with a laboratory model of blood vessel lining provides the most compelling evidence so far that a specific trio of cells is required for the spread of breast cancer. The findings could lead to better tests for predicting whether a woman’s breast cancer will spread and to new anticancer therapies. The study was published in Science Signaling (2014; doi:10.1126/scisignal.2005329).
In earlier studies involving animal models and human cancer cell lines, researchers found that breast cancer spreads when three specific cells are in direct contact: an endothelial cell, a perivascular macrophage, and a tumor cell that produces high levels of Mena, a protein that enhances a cancer cell’s ability to spread.
Where these three cells come in contact is where tumor cells can enter blood vessels, called a tumor microenvironment of metastasis (TMEM). Tumors with high numbers of TMEM sites (ie, they have a high TMEM score) were more likely to metastasize than were tumors with lower TMEM scores. In addition, the researchers found that cancer tissues high in MenaINV, an invasive form of Mena, were especially likely to metastasize.
“Those studies revealed new insights into how cancer might spread, but they didn’t necessarily show what is happening in patients,” said study leader Maja Oktay, MD, PhD, associate professor of pathology at Albert Einstein College of Medicine Yeshiva University and attending cytopathologist at Montefiore Einstein Center for Cancer Care in New York, New York.
All 100 patients included in this study had been diagnosed with invasive ductal carcinoma and were being treated at MECCC. Invasive ductal carcinoma is the most common type of invasive breast cancer, accounting for 80% of cases. In this disease, the cancer has grown through the duct walls and into the surrounding breast tissue.
For the subset of more recent patients, the researchers assessed tumor cell behavior. In particular, they examined the ability of the cancer cells to cross the endothelium (inner layer) of blood vessels. Biopsied tumor tissue from all 60 new patients was fixed in formalin and embedded in paraffin so that TMEM sites in the tissue could be counted.
“These results confirm that TMEM sites and MenaINV are essential for the spread of breast cancer in humans,” said Oktay. “They also imply that MenaINV expression and TMEM score measure related aspects of a commonly used mechanism that human breast cancers use to metastasize.”
Oktay noted 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.”