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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.

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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

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  1. Andreas D. Hartkopf
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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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