Routine Use Of
Liquid Biopsy Draws Near

Most people are familiar with surgical or needle biopsies in which small pieces of tissue are removed to evaluate for cancer; however, few are knowledgeable about liquid biopsy. A liquid biopsy is the removal of blood, plasma, or other secretions such as stool, to examine for circulating tumor cells or circulating tumor DNA. The most familiar use of liquid biopsy is Cologuard®, in which a stool sample is examined for colon cancer DNA. In the case of breast cancer, the liquid biopsy is used to detect minimal residual disease following chemotherapy, which may lead to disease recurrence. It may also help determine who may or may not benefit from additional therapy. Ultimately, the researchers’ question was simple–does the presence of circulating tumor cells or circulating DNA following chemotherapy lead to an increased risk of disease recurrence?

In a recent large multicenter study, researchers compared the use of examining blood for circulating tumor cells (CTCs) versus circulating tumor DNA (ctDNA) in breast cancer patients. The patients chosen had triple-negative breast cancer, a highly aggressive tumor, or had undergone preoperative or neoadjuvant chemotherapy and still had remaining cancer in their breast or lymph nodes following treatment. One hundred forty-two samples of ctDNA were collected, and 123 CTC samples were collected.

Circulating tumor DNA
ctDNA was detected in about two of every three cases and was consistently associated with an inferior distant disease-free survival (DDFS). DDFS is a way that scientists look at survival based solely on the presence or absence of disease at a distant site. At 24 months, DDFS was 56% in ctDNA positive patients compared to 81% in ctDNA negative patients. Disease-free survival (DFS) is a method that researchers use to refer to patients who survive with no evidence of disease either in the breast region or elsewhere. At 24 months of follow-up, the DFS was 50% in patients who were found to have ctDNA versus 76% for those that were negative. With and without recurrent disease, the overall survival was vastly superior in those patients that did not have ctDNA detected in their blood.

Combining circulating tumor cells and circulating tumor DNA with clinical outcomes
CTCs were detected in 43% of all patients. The authors noted that the number of circulating tumor cells was associated with an inferior distant disease-free survival. When combining CTCs and ctDNA, patients who were positive for both had significantly poorer outcomes compared to those who were positive for either CTCs or ctDNA alone. The patients negative for both had the best results compared to all other groups.

The authors noted that “the post neoadjuvant setting needs improvement, particularly in the subgroup with residual disease” following surgery. This study demonstrates that patients with triple-negative breast cancer who have residual disease following neoadjuvant or preoperative chemotherapy can be stratified using ctDNA and CTCs as to the patient’s risk of having minimal residual disease. This minimal residual disease can lead to major metastatic deposits and ultimately to death. This study suggests that patients who are negative for ctDNA and CTCs may be ideal for de-escalation, additional chemotherapy after surgery. Of equal importance are those patients who test positive for either circulating tumor cells or DNA, representing an extremely high-risk subgroup that is likely to be good candidates for additional systemic therapies.