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Leucocyte nadir as a marker for chemotherapy efficacy in node-positive breast cancer treated with adjuvant CMF
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  • Open access
  • Published: 09 July 1999

Leucocyte nadir as a marker for chemotherapy efficacy in node-positive breast cancer treated with adjuvant CMF

  • P Poikonen1,
  • T Saarto1,
  • J Lundin2,
  • H Joensuu1 &
  • …
  • C Blomqvist1 

British Journal of Cancer volume 80, pages 1763–1766 (1999)Cite this article

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Summary

The purpose of this study was to examine the association between the leucocyte nadir and prognosis in breast cancer patients receiving adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF). Three hundred and sixty-eight patients with node-positive breast cancer without distant metastases were treated with six cycles of adjuvant CMF. Some patients (n = 60) also received tamoxifen. All patients underwent surgery and received radiotherapy to the axillary and supraclavicular lymph nodes and the chest wall. The effect of leucopenia caused by CMF on distant disease-free survival (DDFS) and overall survival (OS) was assessed. A low leucocyte nadir during the chemotherapy was associated with a long DDFS in univariate analysis when tested as a continuous variable (the relative risk (RR) 1.3, 95% confidence interval (CI) 1.04–1.06, P = 0.02). Similarly, when the leucocyte nadir count was divided into tertiles, the patients who had the highest nadir values during the six-cycle treatment had worst outcome (RR 1.6, 95% CI 1.07–2.5, P = 0.02). However, in a multivariate analysis only the number of affected lymph nodes, tumour size, progesterone receptor status, surgical procedure, age and adjuvant tamoxifen therapy retained prognostic significance, whereas the leucocyte nadir count did not. A low leucocyte nadir during the adjuvant CMF chemotherapy is associated with favourable DDFS and it may be a useful biological marker for chemotherapy efficacy.

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  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  • Ahmann, D. L., O’Fallon, J. R., Scanlon, P. W., Payne, W. S., Bisel, H. F., Edmonson, J. H., Frytak, S., Hahn, R. G., Ingle, J. N., Rubin, J. & Creagan, E. T. (1982). A preliminary assessment of factors associated with recurrent disease in a surgical adjuvant clinical trial for patients with breast cancer with special emphasis on the aggressiveness of therapy. Am J Clin Oncol 5: 371–381.

    Article  CAS  Google Scholar 

  • Ang, P. T., Buzdar, A. U., Smith, T. L., Kau, S. & Hortobagyi, G. N. (1989). Analysis of dose intensity in doxorubicin-containing adjuvant chemotherapy in stage II and III breast carcinoma. J Clin Oncol 7: 1677–1684.

    Article  CAS  Google Scholar 

  • Bonadonna, G. & Valagussa, P. (1981). Dose–response effect of adjuvant chemotherapy in breast cancer. N Engl J Med 304: 10–15.

    Article  CAS  Google Scholar 

  • Colleoni, M., Price, K., Castiglione-Gertch, A., Goldhirch, A. & Coates, A. (1998). Dose–response effect of adjuvant cyclophosphamide, methotrexate, 5-fluorouracil (CMF) in node-positive breast cancer. Eur J Cancer 34: 1693–1700.

    Article  CAS  Google Scholar 

  • Cox, D. (1972). Regression models and life tables. J R Statist Soc Ser B34: 187–220.

    Google Scholar 

  • Early Breast Cancer Trialists’ Collaborative Group (1992). Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy: 133 randomised trials involving 31 000 recurrences and 24 000 deaths among (1999) 75 000 women. Lancet 339: 1–15

  • Fisher, B., Anderson, S., Wickerham, D. L., DeCillis, A., Dimitrov, N., Mamounas, E., Wolmark, N., Pugh, R., Atkins, J. N., Meyers, F. J., Abramson, N., Wolter, J., Bornstein, R. S., Levy, L., Romond, E. H., Caggiano, V., Grimaldi, M., Jochimsen, P. & Deckers, P. (1997). Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22. J Clin Oncol 15: 1858–1869.

    Article  CAS  Google Scholar 

  • Fumoleau, P., Devaux, Y., Vo, V. M., Kerbrat, P., Fargeot, P., Schraub, S., Mihura, J., Namer, M. & Mercier, M. (1993). Premenopausal patients with node-positive resectable breast cancer. Preliminary results of a randomised trial comparing 3 adjuvant regimens: FEC 50 × 6 cycles vs FEC 50 × 3 cycles vs FEC 75 × 3 cycles. The French Adjuvant Study Group. Drugs 2: 38–45.

    Article  Google Scholar 

  • Glucksberg, H., Rivkin, S. E., Rasmussen, S., Tranum, B., Gad, E. l., Mawla, N., Costanzi, J., Hoogstraten, B., Athens, J., Maloney, T., McCracken, J. & Vaughn, C. (1982). Combination chemotherapy (CMFVP) versus L-phenylalanine mustard (L-PAM) for operable breast cancer with positive axillary nodes: a Southwest Oncology Group Study. Cancer 50: 423–434.

    Article  CAS  Google Scholar 

  • Howell, A., Rubens, R. & Bush, H. (1984). A controlled trial of adjuvant chemotherapy with melphalan versus cyclophosphamide, methotrexate and fluorouracil for breast cancer. Resent Results Cancer Res 96: 74–89.

    Article  CAS  Google Scholar 

  • Kaplan, E. & Meier, P. (1958). Non-parametric estimation from incomplete observations. J Am Statist Assoc 53: 457–481.

    Article  Google Scholar 

  • Longo, D. L., Duffey, P. L., DeVita, V. J., Wesley, M. N., Hubbard, S. M. & Young, R. C. (1991). The calculation of actual or received dose intensity: a comparison of published methods. J Clin Oncol 9: 2042–2051.

    Article  CAS  Google Scholar 

  • Mouridsen, H. T., Rose, C., Brincker, H., Thorpe, S. M., Rank, F., Fischerman, K. & Andersen, K. W. (1984). Adjuvant systemic therapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group’s trials of cyclophosphamide or CMF in premenopausal and tamoxifen in postmenopausal patients. Recent Results Cancer Res 96: 117–128.

    Article  CAS  Google Scholar 

  • Peto, R., Pike, M. & Armitage, P. (1977). Dosing and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer 35: 1–39.

    Article  CAS  Google Scholar 

  • Pronzato, P., Campora, E., Amoroso, D., Bertelli, G., Botto, F., Conte, P. F., Sertoli, M. R. & Rosso, R. (1989). Impact of administration-related factors on outcome of adjuvant chemotherapy for primary breast cancer. Am J Clin Oncol 12: 481–485.

    Article  CAS  Google Scholar 

  • Redmond, C., Fisher, B. & Wieand, H. S. (1983). The methodologic dilemma in retrospectively correlating the amount of chemotherapy received in adjuvant therapy protocols with disease-free survival. Cancer Treatment Rep 67: 519–526.

    CAS  Google Scholar 

  • Rodriguez, K. R., Hortobagyi, G. N., Buzdar, A. U. & Blumenschein, G. R. (1981). Combination chemotherapy for breast cancer metastatic to bone marrow. Cancer 48: 227–232.

    Article  Google Scholar 

  • Saarto, T., Blomqvist, C., Rissanen, P., Auvinen, A. & Elomaa, I. (1997). Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer. Br J Cancer 75: 301–305.

    Article  CAS  Google Scholar 

  • Senn, H., Jungi, W. & Amgewerd, R. (1984). Adjuvant chemoimmunotherapy with LMF + BCG in node-negative and node positive breast cancer. 8 year results. Recent Results Cancer Res 96: 90–101.

    Article  CAS  Google Scholar 

  • Tormey, D., Gelman, R. & Falkson, G. (1983). Prospective evaluation of rotating chemotherapy in advanced breast cancer. An Eastern Cooperative Oncology Group Trial. Am J Clin Oncol 6: 1–18.

    Article  CAS  Google Scholar 

  • Velez-Garcia, E., Carpenter, J. & Moore, M. (1987). Postsurgical adjuvant chemotherapy with or without radiotherapy in women with breast cancer and positive axillary nodes: Progress report of Southeastern Cancer Study Group (SEG) trial. Adjuvant Ther Cancer V: 347–355.

    Google Scholar 

  • Wood, W. C., Budman, D. R., Korzun, A. H., Cooper, M. R., Younger, J., Hart, R. D., Moore, A., Ellerton, J. A., Norton, L., Ferree, C. R., Colangelo Ballow, A., Frei, III E. & Henderson, C. (1994). Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. N Engl J Med 330: 1253–1259.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Oncology, Helsinki University Central Hospital, PO Box 180, Helsinki, FIN-00029 HYKS, Finland

    P Poikonen, T Saarto, H Joensuu & C Blomqvist

  2. HUCH Clinical Research Institute, Helsinki, Finland

    J Lundin

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  1. P Poikonen
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  2. T Saarto
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  3. J Lundin
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  4. H Joensuu
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  5. C Blomqvist
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From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

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Poikonen, P., Saarto, T., Lundin, J. et al. Leucocyte nadir as a marker for chemotherapy efficacy in node-positive breast cancer treated with adjuvant CMF. Br J Cancer 80, 1763–1766 (1999). https://doi.org/10.1038/sj.bjc.6690594

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  • Received: 11 March 1998

  • Revised: 03 October 1998

  • Accepted: 20 November 1998

  • Published: 09 July 1999

  • Issue date: 01 August 1999

  • DOI: https://doi.org/10.1038/sj.bjc.6690594

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Keywords

  • adjuvant chemotherapy
  • breast neoplasms
  • CMF
  • leucopenia

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