Writing about their findings in an early online issue of The Lancet Oncology, researchers from The University of Texas MD Anderson Cancer Center note that, thanks partly to research they had done before, we already know the presence of CTCs in the blood correlates with a poor prognosis once breast cancer has spread to other parts of the body (metastatic breast cancer).
Now their latest study, one of the first and largest of its kind, shows CTCs may have a similar predictive value in the early stages of the disease.
Many patients who have treatment for early stage breast cancer that has not spread, have the tumor and lymph nodes surgically removed and then undergo chemotherapy and radiotherapy to remove all traces of the disease.
But, around two years later, a peak time for recurrence, says first author Anthony Lucci, professor in MD Anderson's Department of Surgical Oncology, around one third of these patients will experience a return of the cancer in another part of the body.
Lucci told the press, "we wanted to understand why".
He said they found that "cancer cells can break free of the primary tumor very early on, and even the earliest stage cancers can shed these dangerous cells."
"We can now reliably detect circulating tumor cells in 25 percent of non-metastatic breast cancer patients with no evidence of disease, and know that their risk of recurring or dying is around four times higher than those without these cells in their blood circulation," said Lucci.
In their background notes, the researchers write that in the case of metastatic breast cancer, the presence and higher numbers of CTCs links strongly with earlier time to recurrence and poor overall survival. And studies have shown this is also the case in metastatic colorectal and prostate cancers.
The push to discover if this is true of earlier stage cancer has been going on for a while. Currently, axillary lymph node dissection is the one of the best predictors of prognosis for women with early stage breast cancer.
Lucci and colleagues collected CTCs from blood and bone samples of 302 breast cancer patients of average age 54, and whose cancer was in Stage I, Stage II and Stage III. All patients were being treated at MD Anderson, and none had undergone chemotherapy before giving the samples.
Patients with cancer in more than one breast, or who had another cancer within five years of their breast cancer diagnosis, were not included.
For this study, the researchers only used data on the blood CTCs, not the bone marrow CTCs.
They used a system called Veridex Cell Search to detect and measure the CTCs. They then correlated the results with tumor characteristics, such as size and grade; hormone status (estrogen, progesterone and HER2); and the extent of lymph node involvement.
They followed the patients for a median period of 35 months, and carried out statistical tests to find any links between CTC measurements and progression-free and overall survival.
- Detection of one or more CTCs predicted both decreased progression-free survival, or early disease recurrence, and overall survival.
- 15% of patients who had at least one CTC, relapsed (that is 11 out of 73 women).
- This compared with a relapse rate of 3% among those who had no detected CTCs (7 out of 229).
- The more CTCs detected, the lower the progression-free survival and overall survival.
- After two years of follow-up, the progression-free survival in patients with no CTCs was 98%.
- This compared with 87% for patients with 1 or more CTCs, 79% for those with 2 or more CTCs, and 69% for those with 3 or more CTCs.
"The presence of one or more circulating tumour cells predicted early recurrence and decreased overall survival in chemonaive patients with non-metastatic breast cancer. These results suggest that assessment of circulating tumour cells might provide important prognostic information in these patients."
Lucci said it was interesting that none of the other primary tumor characteristics, including size, accurately predicted whether they would find CTCs.
He said they are now going to try and find out which CTCs establish metastasis away from the primary site, and which do not survive outside of this area.
It is early days to start changing practice based on these findings. More research, such as a larger, multi-center trial must now be done to confirm these results. Only then can work begin to see if detecting CTCs is a valid test for deciding what type of treatment early stage breast cancer patients should undergo, said Lucci.
Funds from the Society of Surgical Oncology Clinician Investigator Award, The Morgan Welch Inflammatory Breast Cancer Program, The Institute for Personalized Cancer Therapy and the State of Texas Rare and Aggressive Breast Cancer Research Program, helped pay for the study.
Written by Catharine Paddock PhD