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. 2017 Dec;166(3):695-700.
doi: 10.1007/s10549-017-4452-9. Epub 2017 Aug 16.

Molecular characterization and heterogeneity of circulating tumor cells in breast cancer

Anna Jakabova  1 , Zuzana Bielcikova  2 , Eliska Pospisilova  1 , Rafal Matkowski  3   4 , Bartlomiej Szynglarewicz  3   4 , Urszula Staszek-Szewczyk  3   4 , Milada Zemanova  2 , Lubos Petruzelka  2 , Petra Eliasova  1 , Katarina Kolostova  1 , Vladimir Bobek  5   6   7   8   9
Affiliations

Molecular characterization and heterogeneity of circulating tumor cells in breast cancer

Anna Jakabova et al. Breast Cancer Res Treat. 2017 Dec.

Abstract

Introduction: This study analyzes peripheral blood samples from breast cancer (BC) patients. CTCs from peripheral blood were enriched by size-based separation and were then cultivated in vitro. The primary aim of this study was to demonstrate the antigen independent CTC separation method with high CTC recovery. Subsequently, CTCs enriched several times during the treatment were characterized molecularly.

Methods: Patients with different stages of BC (N = 167) were included into the study. All patients were candidates for surgery, surgical diagnostics, or were undergoing chemotherapy. In parallel, 20 patients were monitored regularly and in addition to CTC presence, also CTC character was examined by qPCR, with special focus on HER2 and ESR status.

Results: CTC positivity in the cohort was 76%. There was no significant difference between the tested groups, but the highest CTC occurrence was identified in the group undergoing surgery and similarly in the group before the start of neoadjuvant treatment. On the other hand, the lowest CTC frequencies were observed in the menopausal patient group (56%), ESR+ patient group (60%), and DCIS group (44.4%). It is worth noting that after completion of neoadjuvant therapy (NACT) CTCs were present in 77.7% of cases. On the other hand, patients under hormonal treatment were CTC positive only in 52% of cases.

Discussions: Interestingly, HER2 and ESR status of CTCs differs from the status of primary tumor. In 50% of patients HER2 status on CTCs changed not only from HER2+ to HER2-, but also from HER2- to HER2+ (33%). ESR status in CTCs changed only in one direction from ESR+ to ESR-.

Conclusions: Data obtained from the present study suggest that BC is a heterogeneous disease but CTCs may be detected independently of the disease characteristics in 76% of patients at any time point during the course of the disease. This relatively high CTC occurrence in BC should be considered when planning the long-term patient monitoring.

Keywords: Breast cancer; CTCs; Circulating tumor cells; Cultivation; Gene expression; In vitro; MetaCell.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
CTCs isolated from a patient with breast cancer, captured on the separation membrane (vital fluorescent staining— NucBlue® and Celltracker®). Bar represents 10 µm
Fig. 2
Fig. 2
CTC positivity in relation to menopausal stage and primary tumor HR− expression
Fig. 3
Fig. 3
CTC positivity in relation to menopausal stage and primary tumor HR and HER2− expression
See this image and copyright information in PMC

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