What Is a Circulating Tumor Cell?

Sometimes, a solid primary tumor can shed cells into the blood and lymph vessels. These cells are then carried around the body. They are individually referred to as circulating tumor cells (CTCs) but they can also exist as clusters (CTC clusters).

CTCs can be seeds for additional tumors to grow in other parts of the body. These tumors are called metastases. After metastasis, cancer is much more difficult to treat because all the tumors must be located, and the effect of chemotherapy, radiotherapy, and surgery on multiple organs must be considered.

Note that not every CTC becomes a seed for an additional tumor and the presence of CTCs does not automatically mean that metastasis has occurred. CTCs are not currently considered within definitions of the stages or grades of cancer. In fact, there are indications that CTCs can be shed during all stages of cancer.

What Are the Stages and Grades of Cancer?

As you may know, part of the diagnostic process for cancer involves defining the stage and/or grade. This information helps in informing the treatment regime. Staging defines how advanced the cancer is; grading defines the cell behavior. Information on the size and number of tumors can also be used to determine the tumor load or tumor burden.

One staging system involves defining stages 0 through IV:

• Stage 0 and stage I cancer, respectively, mean a very small or small tumor located on only one organ. Stage 0 tumors may not require immediate treatment, just monitoring.
• Stage II and stage III mean that the tumor is growing and may push into or spread to surrounding tissues and lymph nodes. With most cancers, stage II does not involve any actual spread to the surrounding tissues or lymph nodes, but note that the definition of stage II can vary depending on the tumor type, creating some overlap between these categories.
• Stage IV cancer is when the cancer has spread to other organs. The new tumors (metastases) are distant from the primary tumor and, due to differences in the organ where they arose, can have different characters.

Another staging system is the TNM system:

• T1–4 to indicate the size of the primary tumor;
• N0–3 to indicate the number of lymph nodes affected; and
• M0 or M1 to indicate the absence or presence of metastases.

The grading system in common use defines cancer cells as grade 1, 2, or 3. Those that resemble normal cells and have a normal growth rate are grade 1. When the appearance and growth rate change, the grade increases, with grade 3 indicating abnormal appearance and aggressive spreading due to a high growth rate.

What about Genetic Information?

Other information is of course essential to make informed treatment decisions. We know that there can be significant genetic differences between tumors of the same organs in different people. This relates to the possibility to investigate the tumor mutational burden: the number of non-inherited mutations in the cells of a tumor. It is also important for looking at what receptors the tumor cells are expressing, which influences treatment decisions.

For example, when considering the breast cancer called ductal carcinoma, physicians want to know if the tumor is estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), human epidermal growth factor receptor 2-positive (HER2+), or triple-negative. This information is normally obtained by taking a biopsy directly from the tumor, which can be an invasive and painful process.

What Is the Value of CTCs?

CTCs come from the tumor and therefore carry genetic information about it. They can therefore be used for a process called a liquid biopsy, which is a less invasive way to gather information about a cancer. Rather than taking a solid biopsy directly from the tumor, blood can be drawn and analyzed for CTCs.

However, CTCs are rare. Are there enough to guarantee accurate diagnostic information?

This Study on CTCs Yielded Promising Results

The study detailed in “Preliminary Clinical Validation of a Filtration-Based CTC Assay for Tumor Burden and HER2 Status Monitoring in Metastatic Breast Cancer” is just one of many currently looking at clinically valuable information from CTCs. In this study, blood samples from 47 patients with metastatic breast cancer were analyzed for tumor burden and HER2 status using a new method. The preliminary results indicate that tumor burden and HER2 status can be successfully determined from CTCs. The assay requires further clinical validation, but this is very promising.

Such studies are common, especially since emerging technologies are making it easier to detect and analyze CTCs. If CTC assays can help to determine tumor burden, tumor mutational burden, or even define the grade of a cancer, then liquid biopsies could become a commonplace diagnostic technique.

Crucially, there are studies looking into the possibility of CTCs being used for early diagnosis of cancer, since they can even be shed by stage I solid tumors. Suggestions of using a routine blood test to check for the presence of common cancers have been made. We may be on the verge of an important new phase in cancer diagnosis and treatment.

Note: This post is based on an article that is not open-access; i.e., only the abstract is freely available. Please also note that one of the authors of the paper declared that they are a full-time employee of a biotech company. It is normal for authors to declare this in case it might be perceived as a conflict of interest.