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An increase in cell number at completion of therapy may develop as an indicator of early relapse

Quantification of circulating epithelial tumor cells (CETC) for monitoring of adjuvant therapy in breast cancer

  • Original Paper
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Abstract

Purpose

Treatment efficiency of adjuvant therapy in breast cancer is only revealed after several years by statistical evaluation and gives no answer for the individual patient. We here present a method to analyze the response to adjuvant chemotherapy online in individual patients.

Methods/results

In 25 consecutive non-metastatic primary breast cancer patients adjuvant fluorouracil/epirubicin/cyclophosphamid (FEC) or EC followed by taxane (EC-T) or cyclophosphamid/methotrexate/fluorouracil (CMF) therapy were given. Circulating epithelial tumor cells (CETC) were quantified before and after each second cycle of the therapy regimen, between the anthracycline and the taxane block of the regimen and in some cases repeatedly during CMF treatment. Independent of the initial cell number CETC numbers showed a decline, no change or a minor increase in 15 patients of which 14 remained in complete remission and 1 suffered local relapse. Ten patients showed an increase at the end of therapy of which 4 have relapsed during the observation time of between 2 months and up to 54 months. This patient group was compared to a previously published group of 25 patients who have all reached a follow-up of 4.5 years or until relapse.

Conclusion

As in the previous report, Kaplan–Meier analysis revealed a high correlation between the response of CETC to therapy and relapse (p < 0.0001) and curves of both patient groups were super imposable. Multivariate analysis revealed the response of CETC to therapy to be an independent predictive marker for relapse.

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References

  • Bonadonna G, Moliterni A, Zambetti M, Daidone MG, Pilotti S, Gianni L, Valagussa P (2005) 30 years’ follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study. BMJ 330:217–220

    Article  PubMed  Google Scholar 

  • Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC, Schlimok G, Diel IJ, Gerber B, Gebauer G, Pierga JY, Marth C, Oruzio D, Wiedswang G, Solomayer EF, Kundt G, Strobl B, Fehm T, Wong GY, Bliss J, Vincent-Salomon A, Pantel K (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353:793–802

    Article  PubMed  CAS  Google Scholar 

  • Campone M, Fumoleau P, Bourbouloux E, Kerbrat P, Roche H (2005) Taxanes in adjuvant breast cancer setting: which standard in Europe? Crit Rev Oncol Hematol 55:167–175

    Article  PubMed  Google Scholar 

  • Carrick S, Parker S, Wilcken N, Ghersi D, Marzo M, Simes J (2005) Single agent versus combination chemotherapy for metastatic breast cancer. Cochrane Database Syst Rev. Apr 18:CD003372

  • Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791

    Article  PubMed  CAS  Google Scholar 

  • Ditsch N, Funke I, Mayer B, Untch M (2002) Detection of disseminated tumor cells in bone marrow-currently of no practical therapeutic value. MMW Fortschr Med 144:37–39

    PubMed  CAS  Google Scholar 

  • Fehm T, Becker S, Pergola-Becker G, Kramer B, Gruber I, Sotlar K, Kurek R, Wallwiener D, Solomayer E (2004) Influence of tumor biological factors on tumor cell dissemination in primary breast cancer. Anticancer Res 24:4211–4216

    PubMed  CAS  Google Scholar 

  • Feldman M, Stanford R, Catcheside A, Stotter A (2002) The use of a prognostic table to aid decision making on adjuvant therapy for women with early breast cancer. Eur J Surg Oncol 28:615–619

    Article  PubMed  CAS  Google Scholar 

  • Griffon-Etienne G, Boucher Y, Brekken C, Suit HD, Jain RK (1999) Taxane-induced apoptosis decompresses blood vessels and lowers interstitial fluid pressure in solid tumors: clinical implications. Cancer Res 59:3776–3782

    PubMed  CAS  Google Scholar 

  • Janni W, Rack B, Schindlbeck C, Strobl B, Rjosk D, Braun S, Sommer H, Pantel K, Gerber B, Friese K (2005) The persistence of isolated tumor cells in bone marrow from patients with breast carcinoma predicts an increased risk for recurrence. Cancer 103:884–891

    Article  PubMed  Google Scholar 

  • Jones AL (2005) Reduction in mortality from breast cancer. BMJ 330:205–206

    Article  PubMed  Google Scholar 

  • Lara O, Tong X, Zborowski M, Chalmers JJ (2004) Enrichment of rare cancer cells through depletion of normal cells using density and flow-through, immunomagnetic cell separation. Exp Hematol 32:891–904

    Article  PubMed  Google Scholar 

  • Lobodasch K, Dengler R, Fröhlich F, Rengsberger M, Schubert R, Pachmann U, Pachmann K (2007) Quantification of circulating tumour cells for monitoring of adjuvant therapy in breast cancer: an increase in cell number at completion of therapy is a predictor of early relapse. Breast 16:211–218

    Article  PubMed  Google Scholar 

  • Mansi JL, Gogas H, Bliss JM, Gazet JC, Berger U, Coombes RC (1999) Outcome of primary-breast-cancer patients with micrometastases: a long-term follow-up study. Lancet 354:197–202

    Article  PubMed  CAS  Google Scholar 

  • Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ, Huth JF, Beitsch PD, Leitch M, Hoover S, Euhus D, Haley B, Morrison L, Fleming TP, Herlyn D, Terstappen LW, Fehm T, Tucker TF, Lane N, Wang J, Uhr JW (2004) Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 10:8152–8162

    Article  PubMed  Google Scholar 

  • Muller V, Stahmann N, Riethdorf S, Rau T, Zabel T, Goetz A, Janicke F, Pantel K (2005) Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity. Clin Cancer Res 11:3678–3685

    Article  PubMed  Google Scholar 

  • Naumov GN, Townson JL, MacDonald IC, Wilson SM, Bramwell VH, Groom AC, Chambers AF (2003) Ineffectiveness of doxorubicin treatment on solitary dormant mammary carcinoma cells or late-developing metastases. Breast Cancer Res Treat 82:199–206

    Article  PubMed  CAS  Google Scholar 

  • Pachmann K (2005a) Longtime recirculating tumor cells in breast cancer patients. Clin Cancer Res 11:5657; author reply 5657–5658

    Article  PubMed  Google Scholar 

  • Pachmann U, Pachmann K (2000) Minimale residuale Tumorerkrankung bei soliden epithelialen Tumoren: Neues automatisiertes Analyseverfahren. Dtsch Ärztebl 97(51–52):A-3511

    Google Scholar 

  • Pachmann K, Heiß P, Demel U, Tilz G (2001) Detection and enumeration of minimal numbers of circulating tumour cells in peripheral blood using Laser Scanning Cytometry (LSC®). Clin Chem Lab Med 39:811–817

    Article  PubMed  CAS  Google Scholar 

  • Pachmann K, Camara O, Kavallaris A, Schneider U, Schünemann S, Höffken K (2005b) Quantification of the response of circulating epithelial cells (CETC) to neodadjuvant treatment of breast cancer: a new tool for therapy monitoring. Breast Cancer Res 7:R975–R979

    Article  PubMed  CAS  Google Scholar 

  • Pierga JY, Bonneton C, Vincent-Salomon A, de Cremoux P, Nos C, Blin N, Pouillart P, Thiery JP, Magdelenat H (2004) Clinical significance of immunocytochemical detection of tumor cells using digital microscopy in peripheral blood and bone marrow of breast cancer patients. Clin Cancer Res 10:1392–1400

    Article  PubMed  CAS  Google Scholar 

  • Rolle A, Günzel R, Pachmann U, Willen B, Höffken K, Pachmann K (2005) Increase in number of circulating disseminated epithelial cells after surgery for non-small cell lung cancer monitored by MAINTRAC® is a predictor for relapse: a preliminary report. World J Surg Oncol 3:18

    Article  PubMed  Google Scholar 

  • Sawyers CL (2005) Calculated resistance in cancer. Nat Med 11:824–825

    Article  PubMed  CAS  Google Scholar 

  • Solomayer EF, Diel IJ, Salanti G, Hahn M, Gollan C, Schutz F, Bastert G (2001) The independence of the prognostic impact of tumor cell detection in the bone marrow of primary breast cancer patients. Clin Cancer Res 7:4102–4108

    PubMed  CAS  Google Scholar 

  • Tong X, Melnik K, Braun S, Zborowski M, Chalmers JJ (2006) Detection of disseminated tumor cells in bone marrow of breast cancer patients. 6th International Conference on Scientific and Clinical Applications of Magnetic Carriers May 17th–20th. Krems, Austria

  • Xenidis N, Vlachonikolis I, Mavroudis D, Perraki M, Stathopoulou A, Malamos N, Kouroussis C, Kakolyris S, Apostolaki S, Vardakis N, Lianidou E, Georgoulias V (2003) Peripheral blood circulating cytokeratin-19 mRNA-positive cells after the completion of adjuvant chemotherapy in patients with operable breast cancer. Ann Oncol 14:849–855

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Clinic for Internal Medicine II, Friedrich Schiller University Jena, Jena, Germany

    Katharina Pachmann, Torsten Kroll, Matthias Rengsberger & Rene Schubert

  2. Labor für spezielle Immunhämatologie und Gendiagnostik, Bayreuth, Germany

    Katharina Pachmann & Ulrich Pachmann

  3. Practice for Internal Medicine, Hematology and Oncology, Regensburg, Germany

    Robert Dengler

  4. Womens Hospital Deutsches Rot-Kreuz Krankenhaus, Chemnitz-Rabenstein, Germany

    Kurt Lobodasch & Frank Fröhlich

  5. Department of Experimental Hematology and Oncology, Clinic for Internal Medicine II, Friedrich Schiller Universität Jena, Erlanger Allee 101, 07747, Jena, Germany

    Katharina Pachmann

Authors
  1. Katharina Pachmann
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  2. Robert Dengler
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  3. Kurt Lobodasch
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  4. Frank Fröhlich
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  5. Torsten Kroll
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  6. Matthias Rengsberger
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  7. Rene Schubert
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  8. Ulrich Pachmann
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Correspondence to Katharina Pachmann.

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Pachmann, K., Dengler, R., Lobodasch, K. et al. An increase in cell number at completion of therapy may develop as an indicator of early relapse. J Cancer Res Clin Oncol 134, 59–65 (2008). https://doi.org/10.1007/s00432-007-0248-3

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  • DOI: https://doi.org/10.1007/s00432-007-0248-3

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