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Time to metastatic relapse and breast cancer cells dissemination in bone marrow at metastatic relapse

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Abstract

Breast cancer dissemination can be monitored in patients by detecting circulating and/or disseminated tumor cells. However, bone marrow disseminated tumor cells (BM DTC) may undergo a dormancy during several years before growing (or not) into clinically detectable metastases. We therefore hypothesized that breast cancers which have formed BM DTC in the course of their metastatic growth might exhibit a longer interval before metastatic relapse. We examined the association of DTC detection (cytokeratin 8, 18 or 19 positive epithelial cells with cancerous morphological features), at metastatic relapse, with the metastasis-free interval in breast cancer patients. In the 110 metastatic patients studied, 42% (n = 64/110) were classified as BM DTC-negative. These patients had a significantly shorter metastasis-free interval than BM DTC-positive patients (P = 0.02). In multivariate logistic regression analysis, the metastasis-free interval was an independent predictor of DTC detection (P = 0.02), together with bone metastasis (P = 0.0003) and low tumor grade (grade I or II, P = 0.05). We finally suggest that a faster metastatic process might skip in some patients the BM DTC-associated dormancy step. Dissemination of DTC in other host organ and/or epithelial–mesenchymal transition from cytokeratin-positive to cytokeratin-negative DTC may explain this observation.

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Abbreviations

BM:

Bone marrow

DTC:

Disseminated tumor cells

MNC:

Mononucleated cells

ER:

Estrogen receptor

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Acknowledgments

M. Caly and F. Viard for technical assistance. This work has been supported by the Institut Curie micrometastasis initiative research program funded by individual grants.

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Authors and Affiliations

  1. Department of Medical Oncology, Institut Curie, 26 Rue d’Ulm, 75005, Paris, France

    François-Clément Bidard, Manuel Rodrigues, Véronique Diéras, Laurent Mignot & Jean-Yves Pierga

  2. Department of Pathology, Institut Curie, Paris, France

    Anne Vincent-Salomon, Brigitte Sigal-Zafrani & Xavier Sastre-Garau

  3. Department of Translational Research, Institut Curie, Paris, France

    Marie-France Poupon

  4. University Paris Descartes, Paris, France

    Jean-Yves Pierga

Authors
  1. François-Clément Bidard
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  2. Anne Vincent-Salomon
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  3. Brigitte Sigal-Zafrani
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  4. Manuel Rodrigues
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  5. Véronique Diéras
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  6. Laurent Mignot
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  7. Xavier Sastre-Garau
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  8. Marie-France Poupon
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  9. Jean-Yves Pierga
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Corresponding author

Correspondence to François-Clément Bidard.

Additional information

This work has been presented in part at the 2008 AACR meeting (San Diego, USA).

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Bidard, FC., Vincent-Salomon, A., Sigal-Zafrani, B. et al. Time to metastatic relapse and breast cancer cells dissemination in bone marrow at metastatic relapse. Clin Exp Metastasis 25, 871–875 (2008). https://doi.org/10.1007/s10585-008-9203-1

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  • DOI: https://doi.org/10.1007/s10585-008-9203-1

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