Clinical value of circulating endothelial cells and circulating tumor cells in metastatic breast cancer patients treated first line with bevacizumab and chemotherapy.
BACKGROUND
We investigated whether circulating tumor cells (CTCs) and circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy combined with bevacizumab in metastatic breast cancer patients.


METHODS
In a French substudy of the MO19391 trial, CTC and CEC counts (CellSearch system) at baseline and changes after two cycles of treatment were correlated with time to progression (TtP).


RESULTS
CTC and CEC levels were not correlated in the 67 patients included. At baseline, CTC positivity was a significant prognostic marker for TtP at a threshold of 3 CTC/7.5 ml (P < 0.05) but not at 5 CTC/7.5 ml (P = 0.09). Baseline CEC levels (median 17 CEC/4 ml, range 1-769) were associated with age > or =45 years (P = 0.01), elevated lactate dehydrogenase (P < 0.01) and not with TtP at any threshold. Changes of CTC count during treatment were not a surrogate of TtP, with any of the model tested (threshold based or relative decrease in percent). However, increase in CEC count was associated with improved TtP, at the threshold of 20 CEC/4 ml (P < 0.01).


CONCLUSIONS
Bevacizumab combined with first-line chemotherapy may modify the predictive value of CTC during treatment possibly due to impaired tumor cells intravasation through vessels endothelium. Variations in CEC levels appear to be a promising early surrogate marker of TtP under antiangiogenic treatment.
Bidard
F-C
FC
CirCe Laboratory.
Mathiot
C
C
CirCe Laboratory; Department of Hematology.
Degeorges
A
A
Department of Pharmacology, Institut Curie, Paris.
Etienne-Grimaldi
M-C
MC
Department of Pharmacogenomics, Centre Antoine Lacassagne, Nice.
Delva
R
R
Department of Medical Oncology, Centre Paul Papin, Angers.
Pivot
X
X
Department of Medical Oncology, Centre Hospitalier Universitaire Jean Minjoz, Besançon.
Veyret
C
C
Department of Medical Oncology, Centre Henri Becquerel, Rouen.
Bergougnoux
L
L
Department of Biostatistics, Roche, Neuilly sur Seine.
de Cremoux
P
P
Department of Pharmacology, Institut Curie, Paris.
Milano
G
G
Department of Pharmacogenomics, Centre Antoine Lacassagne, Nice.
Pierga
J-Y
JY
CirCe Laboratory; Université Paris Descartes, Paris, France. Electronic address: jean-yves.pierga@curie.net.
D000230:Adenocarcinoma / Q000097:blood* / Q000188:drug therapy*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D000077143:Docetaxel; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000187:drug effects / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage; D011446:Prospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D000077143:Docetaxel; D000068258:Bevacizumab; D017239:Paclitaxel