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Breast Cancer Res Treat. 2016 Nov;160(2):277-290. Epub 2016 Oct 1.

Impact of apoptotic circulating tumor cells (aCTC) in metastatic breast cancer.

Author information

1
National Center for Tumor Diseases, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany.
2
Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
3
Department of Obstetrics and Gynecology, University of Tübingen, Calwerstraße7, 72076, Tübingen, Germany.
4
Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany.
5
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
6
Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
7
Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany. markus.wallwiener@med.uni-heidelberg.de.

Abstract

PURPOSE:

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 CTCBL to one completed treatment cycle for their utility in predicting response, progression-free survival (PFS), and overall survival (OS) in MBC.

METHODS:

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). CTCKIN were characterized by ≥25 % changes in CTC counts.

RESULTS:

Numbers of iCTC and aCTC at baseline correlated strongly (r = 0.7). For iCTCBL positive patients, additional detection of aCTCBL had a significant prognostic impact on OS (aCTCBL positive 10.3 vs. aCTCBL negative 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 aCTCKIN showed 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).

CONCLUSIONS:

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 aCTCKIN at ≥ 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.

KEYWORDS:

Apoptotic circulating tumor cell; Circulating tumor cell; Kinetic; Metastatic breast cancer; Survival; Treatment response

PMID:
27696083
DOI:
10.1007/s10549-016-3997-3
[Indexed for MEDLINE]

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