Annals of Surgical Oncology

, Volume 14, Issue 6, pp 1896–1903 | Cite as

Association of the Presence of Bone Marrow Micrometastases with the Sentinel Lymph Node Status in 410 Early Stage Breast Cancer Patients: Results of the Swiss Multicenter Study

  • Igor Langer
  • Ulrich Guller
  • Ossi R. Koechli
  • Gilles Berclaz
  • Gad Singer
  • Gabriel Schaer
  • Mathias K. Fehr
  • Thomas Hess
  • Daniel Oertli
  • Lucio Bronz
  • Beate Schnarwyler
  • Edward Wight
  • Urs Uehlinger
  • Eduard Infanger
  • Daniel Burger
  • Markus Zuber
Article

Abstract

Background

The sentinel lymph node (SLN) status has proven to accurately reflect the remaining axillary lymph nodes and represents the most important prognostic factor. It is unknown whether an association exists between the SLN status and the presence of bone marrow (BM) micrometastases. The objective of the present investigation was to evaluate whether or not such an association exists.

Methods

In the present investigation 410 patients with early stage breast cancer (pT1 and pT2 ≤3cm, cN0) were prospectively enrolled between 1/2000 and 12/2003. All patients underwent SLN biopsy and bone marrow aspiration. The histological examination of the SLN consisted of step sectioning, H&E, and immunohistochemistry (Lu-5, CK 22) staining. Cancer cells in the BM were stained with monoclonal antibodies A45-B/B3 against cytokeratin and counted by an automated computerized digital microscope.

Results

BM micrometastases were detected in 28.8% (118/410) of all patients. The SLN contained metastases in 32.4% (133/410). Overall 51.2% of the patients (210/410) were SLN negative/BM negative and 12.4% (51/410) SLN positive/BM positive. Of all patients, 16.4% (67/410) were SLN negative/BM positive and 20.0% (82/410) SLN positive/BM negative. There was a statistically significant association between the SLN and BM status, both in unadjusted (Fisher’s exact test: P = .004) and multiple logistic regression analysis (P = .007).

Conclusions

In the present investigation a significant association was found between a positive SLN status and the presence of BM micrometastases. Nonetheless, the percentage of non-concordance (SLN negative/BM positive and SLN positive/BM negative) was considerable. The prognostic impact of BM micrometastases in our patient sample remains to be evaluated.

Keywords

Breast cancer Sentinel lymph node Bone marrow micrometastases Correlation Multicenter trial 

Notes

Acknowledgments

Funding through SAKK, the Swiss Group for Clinical Cancer Research, Berne, Switzerland and the Cancer League of Basel-Stadt and Basel-Land, Basel, Switzerland. The authors thank Guido Sauter, MD, pathologist for initiation of the bone marrow protocol and Rosmarie Chaffard, technician at the Institute of Pathology, University Hospital Basel, for her technical assistance with the analysis of the BM aspirates. We also thank Bernadette von Felten, study nurse at the Department of Surgery, University Hospital Basel, for collecting patients’ data.

References

  1. 1.
    Dearnaley DP, Sloane JP, Ormerod MG, et al. Increased detection of mammary carcinoma cells in marrow smears using antisera to epithelial membrane antigen. Br J Cancer 1981; 44:85–90PubMedGoogle Scholar
  2. 2.
    Braun S, Pantel K, Muller 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; 342:525–533PubMedCrossRefGoogle Scholar
  3. 3.
    Braun S, Cevatli BS, Assemi C, et al. Comparative analysis of micrometastasis to the bone marrow and lymph nodes of node-negative breast cancer patients receiving no adjuvant therapy. J Clin Oncol 2001; 19:1468–75PubMedGoogle Scholar
  4. 4.
    Diel IJ, Cote RJ. Bone marrow and lymph node assessment for minimal residual disease in patients with breast cancer. Cancer Treat Rev 2000; 26:53–65PubMedCrossRefGoogle Scholar
  5. 5.
    Mansi JL, Gogas H, Bliss JM, Gazet JC, Berger U, Coombes RC. Outcome of primary-breast-cancer patients with micrometastases: a long-term follow-up study. Lancet 1999; 354:197–202PubMedCrossRefGoogle Scholar
  6. 6.
    Wiedswang G, Borgen E, Schirmer C, Karesen R, Kvalheim G, Nesland JM, Naume B. Comparison of the clinical significance of occult tumor cells in blood and bone marrow in breast cancer. Int J Cancer 2006; 118:2013–9PubMedCrossRefGoogle Scholar
  7. 7.
    Diel IJ, Kaufmann M, Costa SD, et al. Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status. J Natl Cancer Inst 1996; 88:1652–8PubMedCrossRefGoogle Scholar
  8. 8.
    Gebauer G, Fehm T, Merkle E, Jaeger W, Mitze M. Micrometastases in axillary lymph nodes and bone marrow of lymph node-negative breast cancer patients—prognostic relevance after 10 years. Anticancer Res 2003; 23:4319–24PubMedGoogle Scholar
  9. 9.
    De Vita V Jr. Breast cancer therapy: exercising all our options. N Engl J Med 1989; 320:527–9PubMedCrossRefGoogle Scholar
  10. 10.
    Rosen PR, Groshen S, Saigo PE, Kinne DW, Hellman S. A long-term follow-up study of survival in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma. J Clin Oncol 1989; 7:355–66PubMedGoogle Scholar
  11. 11.
    Langer I, Marti WR, Guller U, Moch H, Harder F, Oertli D, Zuber M. Axillary recurrence rate in breast cancer patients with negative sentinel lymph node (SLN) or SLN micrometastases: prospective analysis of 150 patients after SLN biopsy. Ann Surg 2005; 241:152–8PubMedGoogle Scholar
  12. 12.
    Giuliano AE, Haigh PI, Brennan MB, et al. Prospective observational study of sentinel lymphadenectomy without further axillary dissection in patients with sentinel node-negative breast cancer. J Clin Oncol 2000; 18:2553–9PubMedGoogle Scholar
  13. 13.
    Veronesi U, Paganelli G, Viale G, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 2003; 349:546–53PubMedCrossRefGoogle Scholar
  14. 14.
    Turner RR, Chu KU, Qi K, Botnick LE, Hansen NM, Glass EC, Giuliano AE. Pathologic features associated with nonsentinel lymph node metastases in patients with metastatic breast carcinoma in a sentinel lymph node. Cancer 2000; 89:574–81PubMedCrossRefGoogle Scholar
  15. 15.
    Singletary SE, Allred C, Ashley P, et al. Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol 2002; 20:3628–36PubMedCrossRefGoogle Scholar
  16. 16.
    Choesmel V, Anract P, Hoifodt H, Thiery JP, Blin N. A relevant immunomagnetic assay to detect and characterize epithelial cell adhesion molecule-positive cells in bone marrow from patients with breast carcinoma: immunomagnetic purification of micrometastases. Cancer 2004; 101:693–703PubMedCrossRefGoogle Scholar
  17. 17.
    Choesmel V, Pierga JY, Nos C, Vincent-Salomon A, Sigal-Zafrani B, Thiery JP, Blin N. Enrichment methods to detect bone marrow micrometastases in breast carcinoma patients: clinical relevance. Breast Cancer Res 2004; 6:R556–70PubMedCrossRefGoogle Scholar
  18. 18.
    Krag DN, Kusminsky R, Manna E, et al. The detection of isolated tumor cells in bone marrow comparing bright-field immunocytochemistry and multicolor immunofluorescence. Ann Surg Oncol 2005; 12:753–60PubMedCrossRefGoogle Scholar
  19. 19.
    Pantel K, Muller V, Auer M, Nusser N, Harbeck N, Braun S. Detection and clinical implications of early systemic tumor cell dissemination in breast cancer. Clin Cancer Res 2003; 9:6326–34PubMedGoogle Scholar
  20. 20.
    Cote RJ, Rosen PP, Lesser ML, Old LJ, Osborne MP. Prediction of early relapse in patients with operable breast cancer by detection of occult bone marrow micrometastases. J Clin Oncol 1991; 9:1749–56PubMedGoogle Scholar
  21. 21.
    Gebauer G, Fehm T, Merkle E, Beck EP, Lang N, Jager W. 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; 19:3669–74PubMedGoogle Scholar
  22. 22.
    Molino A, Pelosi G, Micciolo R, Turazza M, Nortilli R, Pavanel F, Cetto GL. Bone marrow micrometastases in breast cancer patients. Breast Cancer Res Treat 1999; 58:123–30PubMedCrossRefGoogle Scholar
  23. 23.
    Braun S, Vogl FD, Naume B, et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 2005; 353:793–802PubMedCrossRefGoogle Scholar
  24. 24.
    Fehm T, Becker S, Pergola-Becker G, et al. Influence of tumor biological factors on tumor cell dissemination in primary breast cancer. Anticancer Res 2004; 24:4211–6PubMedGoogle Scholar
  25. 25.
    Yu JJ, Brennan M, Christos P, Osborne MP, Hoda S, Simmons RM. Bone marrow micrometastases and adjuvant treatment of breast cancer. Breast J 2004; 10:181–5PubMedCrossRefGoogle Scholar
  26. 26.
    Trocciola SM, Hoda S, Osborne MP, et al. Do bone marrow micrometastases correlate with sentinel lymph node metastases in breast cancer patients? J Am Coll Surg 2005; 200:720–5PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2007

Authors and Affiliations

  • Igor Langer
    • 1
  • Ulrich Guller
    • 1
  • Ossi R. Koechli
    • 2
  • Gilles Berclaz
    • 3
  • Gad Singer
    • 4
  • Gabriel Schaer
    • 5
  • Mathias K. Fehr
    • 6
  • Thomas Hess
    • 7
  • Daniel Oertli
    • 1
  • Lucio Bronz
    • 8
  • Beate Schnarwyler
    • 9
  • Edward Wight
    • 10
  • Urs Uehlinger
    • 11
  • Eduard Infanger
    • 12
  • Daniel Burger
    • 12
  • Markus Zuber
    • 13
  1. 1.Department of SurgeryUniversity Hospital BaselBaselSwitzerland
  2. 2.Bethanien ClinicZurichSwitzerland
  3. 3.Division of GynecologyUniversity Hospital BerneBerneSwitzerland
  4. 4.Institute of PathologyUniversity Hospital BaselBaselSwitzerland
  5. 5.Department of Obstetrics and GynecologyKantonsspital AarauAarauSwitzerland
  6. 6.Division of GynecologyUniversity Hospital ZurichZurichSwitzerland
  7. 7.Division of GynecologyKantonsspital WinterthurWinterthurSwitzerland
  8. 8.Department of Obstetrics and GynecologyOspedale San GiovanniBellinzonaSwitzerland
  9. 9.Maternité, Stadtspital TriemliZurichSwitzerland
  10. 10.Division of GynecologyUniversity Hospital BaselBaselSwitzerland
  11. 11.Department of Obstetrics and GynecologyKantonsspital BruderholzBinningenSwitzerland
  12. 12.Department of Obstetrics and GynecologyKantonales Spital Sursee-WolhusenWolhusenSwitzerland
  13. 13.Department of SurgeryKantonsspital OltenOltenSwitzerland

Personalised recommendations