Several studies support the clinical relevance of circulating tumour cell enumeration as a means of assessing response status in metastatic breast cancer. The aim of this study was to conduct a comprehensive pooled analysis comprising globally collected individual patient data to further define and explore the role of serial CTC enumeration as a tool for early treatment monitoring patients with advanced breast cancer. The focus of my presentation this week will be on the predictive power of CTCs for overall survival in different breast cancer subtypes.
What were the methods used in the study?
We screened peer-reviewed publications with data on repeated CTC assessment including both baseline and at least one follow-up blood sampling in patients with advanced breast cancer. We only included studies with the FDA-cleared CellSearch technology by Menarini Silicon Biosystems and we then asked investigators to provide individual patient source data for this pooled analysis. All data was baseline, follow-up CTC assessments were included, and the data set then resulted in 4079 individual patient records.
What did you find?
The different findings: first of all we saw that the baseline CTC count was, of course, predictive for overall survival. The median survival time for patients with more circulating tumour cells was much less favourable. However, to see the longitudinal course of the disease, we divided patients into four subgroups depending on the baseline and the follow-up CTC assessment: CTC negative baseline, negative follow-up; negative-positive; positive-negative and positive-positive. The largest group was in 46% of the patients who were CTC positive and stayed positive. Looking at these four subgroups, we saw that patients with persistently CTC negative results had a much longer overall survival of 47 months compared to approximately 18 months in the persistently positive group. The median overall survival from the two other groups did not differ significantly among each other.
What impact do you think this study will have in the clinic?
I think the most important finding of our study was that if we looked at the CTC response, so taking those patients with a positive CTC assessment at the beginning, and then look at whether they responded in terms of becoming negative or stayed CTC positive, we saw a hazard ratio of 0.5. So we know that at the very early timepoint, that’s 29 days after the initiation of the treatment, we saw the possibility for early treatment monitoring. So very early we can say, based on CTC assessment, whether a treatment works yes or no. The process becomes increasingly valuable as we have more and more treatment options.
In my opinion, these results provide clinical validation of CTC monitoring as an early treatment response monitor in advanced breast cancer and suggests the potential for clinical utility therefore.