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Prognostic Value of Disseminated Tumor Cells in the Bone Marrow of Patients with Operable Primary Breast Cancer: A Long-term Follow-up Study

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Detection of disseminated tumor cells (DTC) in primary breast cancer (BC) patients’ bone marrow (BM) seems to be a surrogate marker of tumor spread and an independent prognostic factor for disease-free and overall survival.

Methods

Here we present the largest single-center cohort of patients (n = 1378) with the longest observation time (median 82.0 months). Immunocytochemical staining was performed using murine monoclonal antibody 2E11 with the avidin–biotin complex technique.

Results

At primary surgery, 49 % of patients showed MUC-1 positive cells inside their BM. Patients without BM DTC had significantly more often T1-tumors (P = 0.007) with less often affected axillary lymph nodes (P < 0.001). We observed a significantly higher incidence of distant metastases in DTC positive patients (P < 0.001). This leads to a reduced disease-free survival (P < 0.0001). Furthermore, in DTC positive patients there was a higher mortality rate and, accordingly, a reduced overall survival (P < 0.0001).

Conclusions

Due to the presence of BM DTC, patients with a clinically poorer outcome can be identified at primary surgery. We therefore suggest that DTC analysis can be used as a prognostic factor and monitoring tool in clinical trials. Future study concepts relating to DTC should aim at identification of BC patients who may profit from adjuvant systemic therapy.

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References

  1. Molloy TJ, Bosma AJ, Baumbusch LO, et al. The prognostic significance of tumour cell detection in the peripheral blood versus the bone marrow in 733 early-stage breast cancer patients. Breast Cancer Res. 2011;13:R61.

    Article  PubMed  Google Scholar 

  2. Diel IJ, Kaufmann M, Costa SD, et al. Micrometastatic breast cancer cells in bone marrow at primary surgery—prognostic value in comparison to nodal status. J Natl Cancer Inst. 1996;88:1652–8.

    Article  PubMed  CAS  Google Scholar 

  3. Braun S, Pantel K, Müller P, et al. Cytokeratin positive cells in the bone marrow and survival of patients with stage I, II or III breast cancer. N Engl J Med. 2000;342:525–33.

    Article  PubMed  CAS  Google Scholar 

  4. Mansi JL, Easton D, Berger U, et al. Bone marrow micrometastases in primary breast cancer: prognostic significance after 6 years follow-up. Eur J Cancer. 1991;27:1552–5.

    Article  PubMed  CAS  Google Scholar 

  5. Gebauer G, Fehm T, Merkle E, et al. Epithelial cells in bone marrow of breast cancer patients at time of primary surgery: clinical outcome during long-term follow-up. J Clin Oncol. 2001;19:3669–74.

    PubMed  CAS  Google Scholar 

  6. Harbeck N, Untch M, Pache L, Eiermann W. Tumor cell detection in the bone marrow of breast cancer patients at primary therapy: results of a 3-year median follow-up. Br J Cancer. 1994;69:566–71.

    Article  PubMed  CAS  Google Scholar 

  7. Diel IJ, Kaufmann M, Goerner R, et al. Detection of tumor cells in bone marrow of patients with primary breast cancer: a prognostic factor for distant metastasis. J Clin Oncol. 1992;10:1534–9.

    PubMed  CAS  Google Scholar 

  8. Cote RJ, Rosen PP, Lesser ML, et al. Prediction of early relapse in patients with operable breast cancer by detection of occult bone marrow micrometastases. J Clin Oncol. 1991;9:1749–56.

    PubMed  CAS  Google Scholar 

  9. Gerber B, Krause A, Mueller H, et al. Simultaneous immunohistochemical detection of tumor cells in lymph nodes and bone marrow aspirates in breast cancer and its correlation with other prognostic factors. J Clin Oncol. 2001;19:960–71.

    PubMed  CAS  Google Scholar 

  10. Naume B, Borgen E, Kvalheim G, et al. Detection of isolated tumor cells in bone marrow in early-stage breast carcinoma patients: comparison with preoperative clinical parameters and primary tumor characteristics. Clin Cancer Res. 2001;7:4122–9.

    PubMed  CAS  Google Scholar 

  11. Braun S, Vogl FD, Pantel K. Collaborative group bone marrow micrometastasis. Disseminated tumor cells (DTC) in bone marrow (BM) and clinical outcome: final results of pooled analysis on 10-year survival of 4,703 breast cancer patients. J Clin Oncol. 2005;23(16S, pt 1 of 2):502.

    Google Scholar 

  12. Fehm T, Braun S, Müller V, et al. A concept for the standardized detection of disseminated tumor cells in bone marrow of patients with primary breast cancer and its clinical implementation. Cancer. 2006;107:885–92.

    Article  PubMed  Google Scholar 

  13. Solomayer EF, Diel IJ, Salanti G, et al. Time independence of the prognostic impact of tumor cell detection in bone marrow of primary breast cancer patients. Clin Cancer Res. 2001;7:4102–8.

    PubMed  CAS  Google Scholar 

  14. Domschke C, Neubrech F, Dick M, et al. Intraoperative bone marrow puncture in breast cancer patients: prospective assessment of adverse side-effects. Breast. 2011;20:62–5.

    Article  PubMed  Google Scholar 

  15. McGuckin MA, Walsh MD, Hohn BG, et al. Prognostic significance of MUC1 epithelial mucin expression in breast cancer. Hum Pathol. 1995;26:432–9.

    Article  PubMed  CAS  Google Scholar 

  16. Borgen E, Naume B, Nesland JM, et al. Standardization of the immunocytochemical detection of cancer cells in BM and blood: I. establishment of objective criteria for the evaluation of immunostained cells. Cytotherapy. 1999;1:377–88.

    Article  PubMed  CAS  Google Scholar 

  17. Mansi JL, Gogas H, Bliss JM, et al. Outcome of primary-breast-cancer patients with micrometastases: a long-term follow-up study. Lancet. 1999;354:197–202.

    Article  PubMed  CAS  Google Scholar 

  18. Braun S, Kentenich C, Janni W, et al. Lack of effect of adjuvant chemotherapy on the elimination of single dormant tumor cells in bone marrow of high-risk breast cancer patients. J Clin Oncol. 2000;18:80–6.

    PubMed  CAS  Google Scholar 

  19. Janni W, Vogl FD, Wiedswang G, et al. Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse—a European pooled analysis. Clin Cancer Res. 2011;17:2967–76.

    Article  PubMed  Google Scholar 

  20. Kraemer B, Rothmund R, Banys M, et al. Impaired bone microenvironment: correlation between bone density and presence of disseminated tumor cells. Anticancer Res. 2011;31:4423–8.

    PubMed  CAS  Google Scholar 

  21. Becker S, Becker-Pergola G, Wallwiener D, et al. Detection of cytokeratin-positive cells in the bone marrow of breast cancer patients undergoing adjuvant therapy. Breast Cancer Res Treat. 2006;97:91–6.

    Article  PubMed  CAS  Google Scholar 

  22. Slade MJ, Singh A, Smith BM, et al. Persistence of bone marrow micrometastases in patients receiving adjuvant therapy for breast cancer: results at 4 years. Int J Cancer. 2005;114:94–100.

    Article  PubMed  CAS  Google Scholar 

  23. Hall C, Krishnamurthy S, Lodhi A, et al. Disseminated tumor cells in biologic subtypes of stage I–III breast cancer patients. Ann Surg Oncol. 2010;17:3252–8.

    Article  PubMed  Google Scholar 

  24. Janni W, Hepp F, Rjosk D, et al. The fate and prognostic value of occult metastatic cells in the bone marrow of patients with breast carcinoma between primary treatment and recurrence. Cancer. 2001;92:46–53.

    Article  PubMed  CAS  Google Scholar 

  25. Wiedswang G, Borgen E, Karensen R, et al. The presence of isolated tumor cells in bone marrow three years after the diagnosis in disease free breast cancer patients predicts an unfavorable outcome. Breast Cancer Res Treat. 2003;82 (Suppl 1):S8.

    Google Scholar 

  26. Van’t Vee LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome in breast cancer. Nature. 2002;415:530–6.

    Article  Google Scholar 

  27. Bernards R, Weinberg RA. A progression puzzle. Nature. 2002;418:823.

    Article  PubMed  CAS  Google Scholar 

  28. Balic M, Lin H, Young L, et al. Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res. 2006;12 :5615–21.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Breast Unit, University of Heidelberg, Heidelberg, Germany

    Christoph Domschke MD, Silvia Kalteisen MD, Luisa Mayer MD, Joachim Rom MD, Joerg Heil MD, Christof Sohn MD & Florian Schuetz MD

  2. CGG-Clinic Mannheim, Mannheim, Germany

    Ingo J. Diel MD

  3. Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany

    Stefan Englert

Authors
  1. Christoph Domschke MD
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  2. Ingo J. Diel MD
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  3. Stefan Englert
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  4. Silvia Kalteisen MD
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  5. Luisa Mayer MD
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  6. Joachim Rom MD
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  7. Joerg Heil MD
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  8. Christof Sohn MD
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  9. Florian Schuetz MD
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Corresponding author

Correspondence to Florian Schuetz MD.

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Domschke, C., Diel, I.J., Englert, S. et al. Prognostic Value of Disseminated Tumor Cells in the Bone Marrow of Patients with Operable Primary Breast Cancer: A Long-term Follow-up Study. Ann Surg Oncol 20, 1865–1871 (2013). https://doi.org/10.1245/s10434-012-2814-4

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  • DOI: https://doi.org/10.1245/s10434-012-2814-4

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