Impact of apoptotic circulating tumor cells (aCTC) in metastatic breast cancer.
While intact circulating tumor cells (iCTC) have independent negative prognostic impact on patients with metastatic breast cancer (MBC), the prognostic relevance of apoptotic CTC (aCTC) has not been validated in larger patient cohorts. This study assessed aCTC and iCTC statuses at baseline (CTCBL) and CTC kinetics (CTCKIN) as changes from CTCBLto one completed treatment cycle for their utility in predicting response, progression-free survival (PFS), and overall survival (OS) in MBC.



Status of iCTC and aCTC was prospectively assessed in 442 patients using the CellSearch™ system. Different cutoffs were analyzed both for iCTC and aCTC (≥5, ≥10, ≥25 and ≥50 CTC/7.5 ml). CTCKINwere characterized by ≥25 % changes in CTC counts.



Numbers of iCTC and aCTC at baseline correlated strongly (r = 0.7). For iCTCBLpositive patients, additional detection of aCTCBLhad a significant prognostic impact on OS (aCTCBLpositive 10.3 vs. aCTCBLnegative 16.4 months, p = 0.012). Worst prognosis for OS was observed in patients with ≥50 iCTC/7.5 ml and simultaneously detected aCTC. Determination of aCTCKINshowed stronger discriminating power than iCTCKIN, with higher PFS and OS for the group with decreasing CTCs (PFS 7.7 vs. 6.1; OS 22.2 vs. 16.4).



Intact and aCTC are predictive of outcome in MBC. Apoptotic CTC counts ≥ 5/7.5 ml in conjunction with iCTC at baseline have an independent unfavorable prognostic impact on OS. Decreasing aCTCKINat ≥ 5/7.5 ml in serial enumeration is associated with favorable outcome. Therefore, separate enumeration of iCTC and aCTC is useful in tailoring systemic treatment.
National Center for Tumor Diseases, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany.
Thomas M
TM
Deutsch
Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
Sabine
S
Riethdorf
National Center for Tumor Diseases, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany.
Juliane
J
Nees
Department of Obstetrics and Gynecology, University of Tübingen, Calwerstraße7, 72076, Tübingen, Germany.
Andreas D
AD
Hartkopf
Department of Obstetrics and Gynecology, University of Tübingen, Calwerstraße7, 72076, Tübingen, Germany.
Birgitt
B
Schönfisch
Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany.
Christoph
C
Domschke
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Martin R
MR
Sprick
Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany.
Florian
F
Schütz
Department of Obstetrics and Gynecology, University of Tübingen, Calwerstraße7, 72076, Tübingen, Germany.
Sara Y
SY
Brucker
Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany.
Stefan
S
Stefanovic
Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany.
Christof
C
Sohn
Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
Klaus
K
Pantel
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.|Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Andreas
A
Trumpp
National Center for Tumor Diseases, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany.|Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany.
Andreas
A
Schneeweiss
Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany. markus.wallwiener@med.uni-heidelberg.de.
Markus
0000-0002-4139-9340
M
Wallwiener
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D055815:Young Adult
D014408:Biomarkers, Tumor
Apoptotic circulating tumor cell; Circulating tumor cell; Kinetic; Metastatic breast cancer; Survival; Treatment response