Breast Cancer Research and Treatment

, Volume 147, Issue 2, pp 345–351 | Cite as

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

  • Andreas D. Hartkopf
  • Diana Stefanescu
  • Markus Wallwiener
  • Markus Hahn
  • Sven Becker
  • Erich-Franz Solomayer
  • Tanja N. Fehm
  • Sara Y. Brucker
  • Florin-Andrei Taran
Clinical trial


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.


Metastatic breast cancer Disseminated tumor cell Circulating tumor cell Survival Bone marrow 



Bone marrow


Breast cancer


Confidence interval


Circulating tumor cell


Disseminated tumor cell


Epithelial cell adhesion molecule


Estrogen receptor


Human epidermal growth factor receptor 2


Hormone receptor


International Society for Hematotherapy and Graft Engineering


Metastatic breast cancer


Overall survival


Progesterone receptor



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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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Andreas D. Hartkopf
    • 1
  • Diana Stefanescu
    • 1
  • Markus Wallwiener
    • 2
  • Markus Hahn
    • 1
  • Sven Becker
    • 3
  • Erich-Franz Solomayer
    • 4
  • Tanja N. Fehm
    • 5
  • Sara Y. Brucker
    • 1
  • Florin-Andrei Taran
    • 1
  1. 1.Department of Obstetrics and GynecologyUniversity of TuebingenTuebingenGermany
  2. 2.Department of Obstetrics and GynecologyUniversity of HeidelbergHeidelbergGermany
  3. 3.Department of Obstetrics and GynecologyUniversity of FrankfurtFrankfurtGermany
  4. 4.Department of Obstetrics and GynecologySaarland UniversityHomburgGermany
  5. 5.Department of Obstetrics and GynecologyUniversity of DuesseldorfDuesseldorfGermany

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