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Prognostic value of bone marrow biopsy in operable breast cancer patients at the time of initial diagnosis: Results of a 20-year median follow-up

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Abstract

From May 1975 until May 1980, 128 operable breast cancer patients, clinical stage I–II, had a core bone marrow biopsy (BMB) from the posterior iliac crest as a part of the routine diagnostic work-up at the time of initial diagnosis. The mean age of the patients was 56 years, range 26–93. In a previous study on this material, 10 patients (7.8 per cent) were positive for tumor cells and 118 negative by conventional histopathology of BMB [1]. In 1996 we reexamined all BMB separately at two laboratories, using monoclonal antibodies against cytokeratins AE1—AE3, KL1, CAM 5–2 (DOP), and DC10, BA17 (MCI). The number of extrinsic cells in the bone marrow was graded positive for micrometastases when ≥ 5 cells or suspicious when 1–4 cells per ∼2 × 106 bone marrow cells were found, using high power field magnification. Micrometastases were detected in 17 patients (13.3 per cent) and another 8 patients were classified as suspicious. The presence of micrometastases was correlated to the axillary lymph node stage and primary tumor location. Median follow-up was 20 years. All 17 micrometastatic patients relapsed and died within 6 years of disease progression with evident osseous metastases. There was one disease-free survivor of the 8 patients with suspicious BMB after 17 years of follow-up. The median overall survival was significantly shorter in tumor-cell positive patients, being 1.9 years compared to 11.7 years in the BMB negative and BMB suspicious groups (p < 0.0001). Immunohistochemical analysis of core BMB taken postoperatively may be useful in predicting the prognosis in patients with breast cancer clinical stage I–II.

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References

  1. Ridell B, Landys K: Incidence and histopathology of metastases of mammary carcinoma in biopsics from the posterior iliac crest. Cancer 44: 1782–1788, 1979

    PubMed  Google Scholar 

  2. Nemeto T, Vana J, Bedwani RN: Management and survival of female breast cancer. Cancer 45: 2917–2924, 1980

    PubMed  Google Scholar 

  3. Early Breast Cancer Trialists Collaborative Group: Systemic treatment of early breast cancer: hormonal, cytotoxic, or immune therapy. Lancet 339: 1–15, 75–85, 1992

    Google Scholar 

  4. Galasko CB: Anatomy and pathways of sekeletal metastases. In: Weiss L, Gilberg HA (eds) Bone Metastasis. Hall, Boston, 1981, pp 49–63

    Google Scholar 

  5. DiStefano A, Tachima CK, Yap HY, Hortobagyi GN: Bone marrow metastases without cortical bone involvement in breast cancer patients. Cancer 44: 196–198, 1979

    PubMed  Google Scholar 

  6. Ingle JN, Tormey D, Tan HK: The bone marrow examination in breast cancer. Diagnostic considerations and clinical usefulness. Cancer 41: 670–674, 1987

    Google Scholar 

  7. Mansi JL, Easton D, Berger U, Gazet JC, Ford HT, Dearnaley D, Coombes RC: Bone marrow micrometastases in primary breast cancer. Prognostic significance after 6 year follow-up. Eur J Cancer 27(12): 1552–1555, 1991

    PubMed  Google Scholar 

  8. Funke J, Fries S, Jauch KW: Detection of tumor cells in bone marrow: A deciding aid for adjuvant therapy in node negative patients with breast cancer. Concept for a multicenter study and results of the pilot phase. Chirurg 62(11): 805–809, 1991

    PubMed  Google Scholar 

  9. Mcnard S, Squicciarini P, Luini A, Sacchini V, Rovini D, Tagliabue E, Veronesi P, Salvadori B, Veronesi U, Colnaghi MI: Immunodetection of bone marrow micrometastases in breast carcinoma patients and its correlation with primary tumour prognostic features. Br J Cancer 69(6): 1126–1129, 1994

    PubMed  Google Scholar 

  10. Merkle E, Henke A, Bahr I, Buhner M, Lang N: Tumor cell detection in bone marrow of primary breast cancer patients (Meeting abstract). 18th Int Congress of Chemotherapy. June 27–July 2, 1993, Stockholm, Sweden, p322, 1993

  11. Redding WH, Monaghan P, Imrie SF, Ormerod MG, Gazet J-C, Coombes RC, Clink HMcD, Dearnaley DP, Sloane JP, Powles TJ: Detection of micrometastases in patients with primary breast cancer. Lancet 2: 1271–1274, 1983

    Article  PubMed  Google Scholar 

  12. Diel IJ, Kaufmann M, Foerner R, Costa SD, Kaul S, Bastert G: Detection of tumor cells in bone marrow of patients with primary breast cancer: a prognostic factor for distant metastasis. J Clin Oncol 10: 1534–1539, 1992

    PubMed  Google Scholar 

  13. 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 69: 566–571, 1994

    PubMed  Google Scholar 

  14. TNM-classification of malignant tumours. Union Internationale Contre le Cancer, Geneva, 1972

  15. Landys K: Role of bone and marrow biopsy in monitoring metastasis. In: Stoll BA, Parbhoo S (eds) Bone Metastasis Monitoring and Treatment. Raven Press, New York, 1983, p 153

    Google Scholar 

  16. Lauerová L, Kovarik J, Bártek J, Rejthar A, Vojtsek B: Novel monoclonal antibodies defining epitopes of human cytokeratin molecule. Hybridoma 7: 495–503, 1989

    Google Scholar 

  17. Bártek J, Dubran J, Hallowes RC, Taylor-Papadimitriou J: A subclass of luminal epithelial cells in the human mammary gland defined by antibodies to cytokeratins. J Cell Sci 75: 17–33, 1985

    PubMed  Google Scholar 

  18. Cordell J, Richardson TC, Pulford KAF, Ghosh AK, Gatter KC, Heyderman E, Mason DY: Production of monoclonal antibodies against human epithelial membrane antigen for use in diagnostic immunocytochemistry. Br J Cancer 52: 347–354, 1985

    PubMed  Google Scholar 

  19. Viac J, Reano A, Brochier J, Staquet MJ, Thivolet J: Reactivity pattern of a monoclonal anti-keratin antibody (KL1). J Invest Dermatol 81: 351–354, 1983

    Article  PubMed  Google Scholar 

  20. Woodcock-Mitchell J, Eichner R, Nelson WG, Sun TT: Immunolocalization of keratin polypeptides in human epidermis using monoclonal antibodies. J Cell Biol 95: 580–588, 1982

    Article  PubMed  Google Scholar 

  21. Fisher RA: The logic of inductive inference. J Royal Stat Soc, Series A 98: 39–54, 1935

    Google Scholar 

  22. Kaplan EL, Meier P: Non-parametric estimation from incomplete observation. J Am Stat Assoc 53: 457–481, 1958

    Google Scholar 

  23. Dearnaley DP, Sloane JP, Imrie S, Coombes RC, Ormerod MG, Lumley H, Jones M, Neville AM: Detection fo isolated mammary carcinoma cells in marrow of patients with primary breast cancer. J R Soc Med 76: 339–364, 1983

    PubMed  Google Scholar 

  24. Fields KK, Elfcnbein GJ, Trudeau WL, Perkins JB, Janssen WE, Moscinski LC: clinical significance of bone marrow metastases as detected using the polymerase chain reaction in patients with breast cancer undergoing high-dose chemotherapy and autologous bone marrow transplantation. J Clin Oncol 14(6): 1868–1876, 1996

    PubMed  Google Scholar 

  25. Kirk SJ, Cooper GG, Hoper M, Watt PCH, Roy AD, Odling-Smee W: The prognostic significance of marrow micrometastases in women with early breast cancer. Eur J Surg Oncol 16: 481–485, 1990

    PubMed  Google Scholar 

  26. Courtemanche DJ, Worth AJ, Coupland RW, Rowell JL, MacFarlane JK: Monoclonal antibody LICR-LON-M8 does not predict the outcome of operable breast cancer. Can J Surg 34(1): 21–26, 1991

    PubMed  Google Scholar 

  27. Cote RJ, Rosen PP, Lesen 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 9(10): 1749–1756, 1991

    PubMed  Google Scholar 

  28. Pantel K, Schlimok G, Braun S, Kutter D, Lindemann F, Schaller G, Funke I, Izbicki JR, Riethmuller G: Differential expression of proliferation-associated molecules in individual micrometastatic carcinoma cells. J Natl Cancer Inst 85(17): 1419–1424, 1993

    PubMed  Google Scholar 

  29. Pantel K, Felber E, Schlimok G: Detection and characterization of residual disease in breast cancer. J Hematother 3(4): 315–322, 1994

    PubMed  Google Scholar 

  30. Cartagena N Jr, Susters S, Cabello-Inchausti B: Artifactual distortion of cells simulating small cell carcinoma in the bone marrow. Ann Clin Lab Sci 23(2): 130–136, 1993

    PubMed  Google Scholar 

  31. Mansi JL, Berger U, McDonell T, Pople A, Rayter Z, Gazet JC, Coombes RC: The fate of bone marrow micrometastases in patients with primary breast cancer. J Clin Oncol 74: 445–449, 1989

    Google Scholar 

  32. Schlimok G, Riethmuller G: Detection, characterization and tumorigenicity of disseminated tumor cells in human bone marrow. Semin Cancer Biol 1(3): 207–215, 1990

    PubMed  Google Scholar 

  33. Ginsbourg M, Musset M, Misset JL, Mathé G: Relationship between proliferative activity of bone marrow micrometastases and plasmatic level of a new cancer marker: lipid associated sialic acid (LASA) in human breast cancer. Biomed & Pharmacother 40: 388–391, 1986

    Google Scholar 

  34. Emerman JT, Stingl J, Petersen A, Shiall EJ, Eaves CJ: Selective growth of freshly isolated human breast epithelial cells cultured at low concentrations in the presence or absence of bone marrow cells. Breast Cancer Res Treat 41: 147–159, 1996

    Article  PubMed  Google Scholar 

  35. Kvalheim G, Detection of occult tumour cells in bone marrow and blood in breast cancer patients. Methods and clinical significance. Acta Oncol Suppl 8: 13–18, 1997

    Google Scholar 

  36. Ginsbourg M, Musset M, Misset JL, Genty O, Mathé S: Simultaneous detection in the bone marrow of mammary cancer metastatic cells and of their labelling index as respective markers of the residual minimum submacroscopic disease and its proliferative condition. Biomed Pharmacother 40: 386–388, 1986

    PubMed  Google Scholar 

  37. Mathieu M-CH, Friedman S, Bosq J, Aillou B, Spielmann M, Travagli J-P, Contesso G: Immunohistochemical staging of bone marrow biopsies for detection of occult metastasis in breast cancer. Breast Cancer Res Treat 15: 21–26, 1990

    PubMed  Google Scholar 

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Landys, K., Persson, S., Kovařík, J. et al. Prognostic value of bone marrow biopsy in operable breast cancer patients at the time of initial diagnosis: Results of a 20-year median follow-up. Breast Cancer Res Treat 49, 27–33 (1998). https://doi.org/10.1023/A:1005980919916

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