NEW YORK – An international team of researchers presented evidence at the San Antonio Breast Cancer Symposium this week suggesting that circulating tumor cell (CTC) enumeration can potentially be used to determine metastatic breast cancer patients' prognosis and treatment response earlier than is currently possible with conventional imaging.
Using Menarini Silicon Biosystems' CellSearch CTC enumeration assay, the team, led by Wolfgang Janni, director of the women's clinic at Ulm University Hospital, conducted a meta-analysis of published studies and found that early CTC dynamics were associated with overall survival in different metastatic breast cancer patient subtypes.
In their study, Janni and his team analyzed 32 pooled datasets from peer-reviewed and published studies of 4,079 metastatic breast cancer patients that had baseline and follow-up measurements using the CellSearch assay after initiating endocrine therapy and chemotherapy.
Researchers first divided patients into CTC-positive and CTC-negative cohorts using baseline measurements, and then tracked changes in CTC levels after a median follow-up of 29 days to assess whether these changes were associated with patients' overall survival.
Of 2,961 patients who were CTC-positive at baseline, 1,855 patients remained CTC-positive after starting treatment, and 1,106 patients became CTC-negative. Meanwhile, of the 1,118 patients who were CTC-negative at baseline, 813 remained CTC-negative after treatment and 305 became CTC-positive at follow-up.
The researchers reported that the median overall survival was highest for patients who were CTC-negative at both points (47 months), followed by patients who were positive at baseline and then negative after beginning treatment (32 months), and those who were negative at baseline and then positive at follow-up (30 months). Patients who were CTC-positive at both time points had the worst median overall survival (18 months).
Compared to patients who were CTC-negative at baseline and follow-up, the risk of death was 215 percent greater for patients who were CTC-positive at both time points, the researchers found. Patients who were CTC-positive at baseline and remained so at follow-up had a 51 percent greater risk of death than those who converted to CTC-negative status after treatment.
The team also classified 2,586 patients' primary tumors into subtypes based on known hormone receptor (HR) and HER2 status. Among these patients, 1,513 were deemed to have a luminal-like tumor (estrogen receptor (ER)-positive, HER2-negative), 682 patients had a HER2-positive tumor, and 391 patients had a triple-negative tumor.
Janni highlighted that his team identified similar overall survival trends among patients regardless of the breast cancer subtype. However, when researchers considered tumor subtypes alongside CTC status, there was an association with overall survival.
Among patients with HER2-positive tumors, the CTC-negative/positive and the CTC-positive/positive subgroup showed significantly worse overall survival compared to those in the negative/negative subgroup. In TNBC patients, the positive/positive group had a significantly shorter overall survival compared to the negative/negative cohort.
Janni acknowledged that his team faced certain physical and logistical limitations while collecting data for the meta-analysis. For example, the team selected the CTC-capture cutoff to be one cell because of time-based restrictions.
Still, based on this analysis, the researchers concluded that at a median of 29 days, follow-up CTC assessments strongly predict overall survival in metastatic breast cancer patients.
Breast cancer patients' responses to treatment are typically tracked using conventional imaging, which can detect changes around three months after starting therapy, depending on the subtype.
"The data indicates that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment," Janni said. "These results provide treatment validation of CTC monitoring as an early treatment response marker in advanced breast cancer and suggest the potential for clinical utility."
While noting that CellSearch's non-invasive approach is attractive for the clinical space, Janni said that oncologists will need to access CTC results quickly in to provide added value to conventional imaging.
"We think [CTCs] can be useful in daily practice … [and] in all situations that we'd like to have early treatment monitoring, such as in immuno-oncology [and for guiding use of] checkpoint inhibitors," Janni said. "We can have simple information with imaging later on, but I think there are clinical situations where we'd love to have early information, and we should consider using CTCs in these situations."
During the call, Carlos Arteaga, director of the Simmons Comprehensive Cancer Center at University of Texas Southwestern, pointed out that while CTC platforms such as CellSearch can be useful to oncologists for guiding patients' treatment on one level, CTC enumeration fails to indicate whether "there could be an actionable somatic mutation target … that warns you about a persistent [cancer cell] population you should worry about."
Arteaga therefore encouraged Janni's team to include plasma tumor circulating tumor DNA (ctDNA) analysis in future studies to help guide clinical and therapy decisions. If Janni's group were to incorporate ctDNA analysis in future research, Arteaga said it may lead to a testing paradigm that "is not only prognostic but also predictive as to which drug we should change to."
Janni's team has launched a new seven-year trial in Germany called "SURVIVE," where they will collect blood samples and assess whether liquid biopsy-based surveillance leads to improved prognosis in breast cancer survivors.