Monitoring circulating tumor cell (CTC) levels to predict rapid progression in metastatic breast cancer (MBC): a prospective, multi-institutional trial
Reviewer: Maria Luisa Veronese, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 5, 2004
Presenter: D.F. Hayes
Presenter's Affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI
Type of Session: Scientific
The identification of markers that predict resistance to a treatment early in the course of therapy would allow termination of a futile treatment and initiation of an alternative regimen. Numerous studies investigating the prognostic relevance of circulating tumor cells have been conducted. However, reports of these studies have shown conflicting results and trials involving a large number of patients and long term follow-up are still lacking.
This study is a prospective, multi-institutional clinical trial to investigate whether monitoring circulating tumor cells (CTC) may identify which patients will not benefit from a chosen regimen.
Materials and Methods
- 177 patients with metastatic breast cancer immediately prior to initiating a new chemotherapeutic regimen
- CTC were measured at baseline prior to beginning therapy and monitored every 3-4 weeks for up to six months. (This study reports only on the first measurement)
- 7.5 ml of whole blood were obtained
- CTC were separated by an immunomagnetic technique using EpCAM antibody
- Multi-color fluorescent labeling was then applied to separated cells (DAPI, cytokeratin 8, 18, and CD45)
- Cells were identified as CTC if they stained positive for both DAPI and cytokeratin 8,18 and/or 19 and negative for CD45
- Clinical outcome was determined by the participating clinical sites without knowledge of CTC levels.
- Analyses was first conducted on 102 patients and it was established that the cutoff which best distinguished short progression free survival (PFS) and/or overall survival (OS) was >5 CTC/7.5 ml blood at baseline and first follow up.
- The analyses was validated in the remaining 75 patients
- 87 (49%) patients had >5 CTC at baseline, and 49 (30%) had persistent or newly elevated levels at first follow up.
- Patients with baseline CTC >5 had a significantly shorter PFS (2.4 vs 6.7 months; p=0.0001) and OS (10.1 vs>18 months, p=0.0001)
- Patients with CTC >5 at first follow-up had short PFS (5-6 weeks vs 7.0 months; p=0.0001) and OS (8.2 vs >18 months; p=0.0001).
- PFS and OS for patients with a reduction in CTC to <5 at first follow-up were equivalent to those of patients with <5 CTC at baseline
- Multi-variate analyses showed CTC as the strongest and most significant predictor of poor outcome.
- 49% patients had >5 CTC at baseline and 30%had persistent or newly elevated levels at first follow up
- CTC >5 at baseline were associated to shorter PFS and OS
- CTC >5 at first follow-up predicted shorter PFS and OS
Measurement of circulating tumor cells as prognostic indicator has been investigated in numerous studies. Several issues remain to be clarified: the markers used to detect tumor cells are not specific, it is not clear whether the tumor cells detected in peripheral blood represent true micrometastasis, studies have used different protocols, and finally data on long term follow-up are lacking. This study investigates whether monitoring circulating tumor cells may identify which patients will not benefit from a chosen regimen. A cut off of 5 CTC is established and the study demonstrate a statistical significant association between the number of CTC and PFS and OS. The clinical relevance of these findings are not completely defined and further randomized studies with a larger population are needed.
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