v4n2 - Predicting Treatment Outcomes in Breast Cancer

A cancerous tumor is a community of individual cells, and sometimes as the tumor grows, some of these cells will break away and migrate to a new site in a process called metastasis. In order to reach distant parts of the body, cancer cells must travel through the bloodstream or lymphatic system. These renegade cells gain access to the circulatory system through leaky blood vessels inside the tumor.

Once in the bloodstream they move to distant sites where they can begin to populate other organs, such as the bone or liver. Because cancer cells contain distinct proteins that make them look different from the cells you would normally expect in the circulatory system, like red and white blood cells, the mobile cells can be “seen” and counted by researchers.

The number of circulating tumor cells (CTCs) in the bloodstream can be measured by several different methods. One commercially available method is called CellSearchTM, and is sold by a company called Veridex. The blood test separates the CTCs from other cells using immunological proteins called antibodies, which recognize specific targets on the cancer cells.

The total number of CTCs in the circulation is very small, so this population is first enriched using antibodies labeled with iron. After these antibodies attach to proteins on the surface of the CTCs, these cells can be separated from the rest with a magnet. But because this subpopulation is still contaminated with non-cancer cells, special dyes plus a second set of fluorescently tagged antibodies that recognize different proteins are used to definitively identify the CTCs. The partially purified cells are sent through a machine that detects the fluorescent signal and counts the CTCs in the sample.

Several studies have shown that there is an association between the prognosis of patients with metastatic cancer and the number of CTCs in the bloodstream, both before and during treatment. The cutoff appears to be five CTCs per 7.5 mL of blood, at least in breast cancer. Patients with fewer than five CTCs have a better chance of surviving longer without their disease progressing, while patients with five or more CTCs have a worse prognosis.

The number of CTCs can also be used to predict the response to chemotherapy. If the number of CTCs drops below five after chemotherapy treatment begins, it suggests the therapy is working, but if the number stays above five, or increases, that particular regimen may not be working effectively. In this case, switching to another form of chemotherapy may be better for the patient. An advantage of this approach is the CTC response can be detected as early as three to four weeks after therapy starts, well before a response could be seen by conventional methods like CT (computed tomography) scan or X-ray. This gives doctors a chance to adjust treatments earlier, before the cancer has a chance to progress further.

While the methodology for measuring CTCs is still being tested and optimized, it is likely to become a powerful tool to help physicians make more effective, individualized treatment decisions in the future.