At the San Antonio Breast Cancer Symposium in December 2022, a French group of scientists presented the results of a trial that could help oncologists make better treatment decisions for patients with metastatic breast cancer. According to the trial, counting the number of tumor cells that have broken off the tumor and entered the bloodstream could help doctors choose between endocrine therapy and chemotherapy for patients who have this aggressive form of breast cancer.
Here is a more detailed look at this trial and what the findings could mean for people with metastatic breast cancer.
Previous Research on CTC Count Treatment Decisions
Currently, the decision between the two treatment options is left in the hands of specialists based on their clinical judgment. Endocrine therapy has significantly fewer and less intense side effects than chemotherapy. As a result, many doctors exhaust endocrine therapy options before switching to chemotherapy. Sometimes, however, chemotherapy is the more effective option. Having more information about which treatment option will be most effective will help doctors get patients who would benefit most from chemotherapy started with that course of treatment sooner.
The outcomes presented at the 2022 conference are a five-year follow-up to the trial results published by François-Clément Bidard, MD, PhD, and his colleagues in 2018. In this study, 755 patients were randomly assigned to have either a CTC-based treatment or a clinical-based treatment group. The researchers were trying to determine whether CTC count is a useful assessment tool for information about a patients’ prognosis, and whether this number could be used to help doctors choose between hormone therapy and chemotherapy.
The results of the follow-up support the researchers’ earlier conclusions. In the 2018 trial, patients who received chemotherapy instead of hormone therapy based on CTC counts showed longer survival with no progression of cancer. The CTC-based hormone therapy patients showed a median progression-free survival (PFS) of 10.5 months, compared to 15.5 months for those who received CTC-based chemotherapy.
Using Cancer Cell Count to Guide Treatment Decisions
The researchers evaluated the impact of making treatment decisions based on the patient’s circulating tumor cell count, also known as CTC. This idea is not new to the world of oncology research. There are two decades’ worth of research on the relationship between CTC and the treatment of metastatic breast cancer. Bidard and the research team found that patients with metastatic estrogen receptor (ER)-positive/HER2 negative breast cancer experienced better long-term outcomes when they were treated based on their CTC counts.
Patients were assigned to either a clinically driven arm, in which treatment was determined using the current standard of care, or the research arm, and which CTC counts were used to drive treatment recommendations. Those who received chemotherapy as a first line treatment had a median survival period 16 months longer than those who received endocrine therapy. In addition, the chemotherapy group showed a 47 percent reduction in their risk of death compared to the endocrine therapy patients.
What Are Circulating Tumor Cells?
Circulating tumor cells (CTCs) are tumor cells that have broken off from a primary tumor to circulate in the bloodstream. While CTCs are originally part of the primary tumor, they differ from primary tumor cells in several ways.
CTCs have properties that allow them to break off the primary tumor. These properties also allow the cells to enter the bloodstream and disseminate in clusters, which makes it easier for cancer to spread. CTCs also have features that aid in their ability to initiate the spread of cancer.
Researchers have been investigating the role of CTCs in cancer metastasis for over a century. Until recently, technical challenges made it extremely difficult to isolate CTCs from the comparatively large pool of circulating blood cells. However, over the past two decades, technological advancements have facilitated advancements in this area. Researchers are now able to more thoroughly research the biology of CTCs than they could before. This has led to clinical applications of CTCs in the treatment, response monitoring, and prognosis evaluation of cancer.
How Can Prognostic Biomarkers Improve Treatment?
CTC is an example of a prognostic biomarker, which is a medical characteristic that can be used to predict future clinical events (such as death, disease progression, disease recurrence, or disease progression) in identified populations. Breast cancer genes 1 and 2 (BRCA1/2) mutations are another common example of prognostic biomarkers that are used to evaluate the progression of breast cancer. Researchers can identify these mutations to determine the likelihood of a second breast cancer occurring.
Bidard believes that the 2022 CTC study shows that prognostic biomarkers can be integrated into treatment plans to improve the management and outcomes of patients with metastatic breast cancer.
Limitations of the CTC Count Study
The findings of this study are valuable and could potentially be a springboard for future improvements in the treatment of metastatic breast cancer. However, like most cancer studies, it has limitations. The study was conducted before CDK4/6 inhibitors had been introduced, which are now widely used as a first-line treatment for patients with metastatic ER-positive/HER2-negative breast cancer.
When the researchers designed this trial, they had a choice between single-agent endocrine therapy and chemotherapy as a first-line therapy. Endocrine therapy using CDK4/6 inhibitors is now the front line option for treatment-naive patients. Despite these limitations, the findings presented at the San Antonio Breast Cancer Symposium are encouraging, and it will be interesting to see how this area of research continues to develop.