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Tumor cell dissemination to the bone marrow and blood is associated with poor outcome in patients with metastatic breast cancer

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Abstract

The purpose of this study was to assess the impact of disseminated tumor cells (DTCs) on progression-free and overall survival (OS) in patients with metastatic breast cancer (MBC) and to compare it to simultaneous detection of circulating tumor cells (CTCs) from the blood in a subgroup. Disseminated tumor cells were identified in bone marrow (BM) aspirates by immunocytochemistry (pancytokeratin antibody A45-B/B3) and cytomorphology prior to the beginning of a new-line therapy. CTCs were enumerated by the CellSearch® technology. BM was obtained from 178 patients with MBC; 64/178 (36 %) patients were DTC-positive. Disseminated tumor cells occurred more frequently in patients with visceral metastases (p = 0.020) and ≥2 lines of therapy (p = 0.017). CTCs were assessed in 33 of these patients and 17/33 (52 %) patients had CTC counts ≥5 CTCs/7.5 ml blood. There was no significant association between the DTC and CTC status. Univariate analysis revealed DTC detection as a significant predictor of poor OS (p < 0.001); median OS in DTC-negative versus DTC-positive patients was 52 [95 % confidence interval (CI) 38–67] versus 28 [95 % CI 19–37] months. Moreover, as described previously, patients with ≥5 CTCs/7.5 ml blood were at an increased risk of disease progression (p = 0.026) and death (p = 0.025). Disseminated tumor cells are predictors of poor prognosis in MBC, highlighting the role of tumor cell dissemination into the BM for breast cancer progression. The absence of a significant association between concurrent DTCs and CTCs suggests they might represent different aspects of systemic BC spread.

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Abbreviations

BM:

Bone marrow

BC:

Breast cancer

CI:

Confidence interval

CTC:

Circulating tumor cell

DTC:

Disseminated tumor cell

EpCAM:

Epithelial cell adhesion molecule

ER:

Estrogen receptor

HER2:

Human epidermal growth factor receptor 2

HR:

Hormone receptor

ISHAGE:

International Society for Hematotherapy and Graft Engineering

MBC:

Metastatic breast cancer

OS:

Overall survival

PR:

Progesterone receptor

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Acknowledgments

We are grateful to Silke Duerr-Störzer, Ingrid Teufel, Sabine Hofmeister, Angelika Amman, and Brigitte Neth for excellent technical assistance.

Conflict of interest

All authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Tuebingen, Calwerstraße 7, 72076, Tuebingen, Germany

    Andreas D. Hartkopf, Diana Stefanescu, Markus Hahn, Sara Y. Brucker & Florin-Andrei Taran

  2. Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

    Markus Wallwiener

  3. Department of Obstetrics and Gynecology, University of Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany

    Sven Becker

  4. Department of Obstetrics and Gynecology, Saarland University, Kirrberger Straße 100, 66421, Homburg, Germany

    Erich-Franz Solomayer

  5. Department of Obstetrics and Gynecology, University of Duesseldorf, Moorenstraße 5, 40225, Duesseldorf, Germany

    Tanja N. Fehm

Authors
  1. Andreas D. Hartkopf
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  2. Diana Stefanescu
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Correspondence to Andreas D. Hartkopf.

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Hartkopf, A.D., Stefanescu, D., Wallwiener, M. et al. Tumor cell dissemination to the bone marrow and blood is associated with poor outcome in patients with metastatic breast cancer. Breast Cancer Res Treat 147, 345–351 (2014). https://doi.org/10.1007/s10549-014-3113-5

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  • DOI: https://doi.org/10.1007/s10549-014-3113-5

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