Non-Invasive Biomarkers: Circulating Tumor Cells

Circulating tumor cells (CTCs) are cancerous cells that have detached from the main tumor and have entered the bloodstream through active or passive intravasation.

While CTCs are rare (as low as one in a billion normal blood cells), studies have shown that CTCs in the blood indicate a worse prognosis and higher risk of recurrence in early-stage and metastatic breast cancer patients.

A blood sample is taken from the patient through a blood draw. The quantification and analysis of CTCs are then done through a few possible types of technologies, including enzyme-linked immunosorbent assays (ELISA), immunofluorescence assays, immunomagnetic separation, and reverse transcription polymerase chain reaction (RT-PCR) assays. Analysis of CTCs can also be done based on the physical characteristics of the cells.

CTCs have been investigated for several potential clinical purposes:

• Diagnostic value for early-stage breast cancer

Due to the low frequency of CTCs and difficulty in detection, CTCs currently have a very none to limited diagnostic value for early-stage breast cancer. At this stage of the research, CTCs are not recommended as a marker for early-stage breast cancer diagnosis as there are other more reliable and accurate diagnostic procedures. More sensitive technologies are needed to be able to detect the wide variety of CTCs effectively to be able to be clinically viable as a diagnostic tool.

• Prognostic value for early-stage and metastatic cancer

While CTC detection is rare, the present results suggest a strong prognostic value in the presence of CTCs for early-stage and metastatic breast cancer. Several published papers have demonstrated a poor prognosis for metastatic breast cancer patients that had presented a basal CTC count of more than 5 in 7.5ml of blood. This also suggests a potential predictive value in determining the best treatment methods. However, the clinical utility of CTC detection remains to be investigated in prospective trials. Prior studies to intensify treatment in patients with breast cancer in whom CTCs have been detected have not yet resulted in decreased risk of cancer recurrence.

• Tool to guide treatment in cancer patients

A meta-analysis of the prognostic value of CTCs showed that CTCs detected before, during, and after systemic treatment of breast cancer retained its prognostic value. However, it is still unsure if changing / intensifying systemic treatment in presence of CTCs can help improve patient outcomes or if CTCs are a marker of bad prognosis only.