The number of circulating tumor cells (CTCs) assessed at baseline and about 1 month after cancer-directed treatment was associated with overall survival in patients with metastatic breast cancer, according to findings from a large retrospective pooled analysis reported by Wolfgang Janni, MD, PhD, at the 2020 San Antonio Breast Cancer Symposium (Abstract GS4-08). Monitoring early treatment responses using CTCs was predictive for overall survival in all tumor subtypes: luminal-like, HER2-positive, and triple-negative breast cancer.

Wolfgang Janni, MD, PhD

“Patients with CTC response had significantly increased overall survival. These results provide clinical validation of CTC monitoring as an early treatment response marker in advanced breast cancer and suggest the potential for clinical utility,” said lead author Dr. Janni, of University Hospital Ulm, Germany. Dr. Janni presented these data at a premeeting press conference.

Response to treatment for metastatic breast cancer is typically monitored by conventional imaging, but it takes approximately 3 to 4 months after initiation of treatment for changes to be detectable on scans.

“With the increasing number of treatment options available to patients with metastatic breast cancer, being able to predict and monitor treatment responses rapidly will be critical to aiding treatment decisions. The data from our study indicate that CTC dynamics can predict the trajectory of the disease a little more than 4 weeks after initiating treatment. This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued. It is also very reassuring that CTC dynamics predicted outcomes for all breast cancer subtypes,” stated Dr. Janni.

Study Details

Several studies support the clinical relevance of CTC enumeration as a means of assessing response status in metastatic breast cancer. The study reported by Dr. Janni was a comprehensive pooled analysis of globally collected data to define further and explore the role of serial CTC monitoring as a tool for early treatment monitoring in patients with metastatic breast cancer. The authors sought to provide predictive power of CTC monitoring in different breast cancer subtypes.

Data were pooled from 14 different data sets for a total of 4,079 patients with metastatic breast cancer. CTC status was measured in blood by a CellSearch assay at baseline and a median of 29 days after treatment initiation. Respondents were categorized according to change in CTC status (ie, positive and negative) from baseline to first follow-up.

The largest subset—made up of 1,855 patients—was CTC-positive at baseline and CTC-positive approximately 1 month later (CTC-positive/CTC-positive; 45.5%). The next-largest subset was CTC-positive/CTC-negative and included 1,106 patients (27.1%). A total of 305 patients (7.4%) were CTC-negative/CTC-positive, and 813 patients (19.9%) were persistently CTC-negative (CTC-negative/CTC-negative). The cutoff used for CTC positivity in this study was at least 1 CTC.

Patients who fared the best were persistently CTC-negative, with a median overall survival of 47 months, whereas survival was shortest in the persistently positive subgroup, with a median of 18 months. Median overall survival was 30 months in the CTC-negative/CTC-positive group, and 32 months in the CTC-positive/CTC-negative group.

“The hazard ratios from the negative/positive and the positive/negative groups did not differ significantly,” said Dr. Janni. “The persistently CTC-negative groups had significantly improved overall survival compared with the other three subgroups [P < .0001]. The evidence is clear that survival is improved in CTC responders.”

Looking at CTC responders alone—those who were positive at baseline but negative thereafter—overall survival was improved by 53% in luminal-like breast cancers, 46% in HER2-positive breast cancer, and 59% in triple-negative breast cancer. “These results provide clinical validation of CTC monitoring as an early treatment response marker,” said Dr. Janni.

The study authors concluded: “This large pooled analysis confirms that at a median of 35 days after treatment initiation, follow-up CTC assessments strongly predict overall survival. These results suggest potential clinical utility of CTC monitoring as early response marker in metastatic breast cancer, especially in luminal-like tumors.”