Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Aug;80(11):1763–1766. doi: 10.1038/sj.bjc.6690594

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

P Poikonen 1, T Saarto 1, J Lundin 2, H Joensuu 1, C Blomqvist 1
PMCID: PMC2363113  PMID: 10468293

Abstract

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. © 1999 Cancer Research Campaign

Keywords: adjuvant chemotherapy, breast neoplasms, CMF, leucopenia

Full Text

The Full Text of this article is available as a PDF (79.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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. 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. 1982 Aug;5(4):371–381. doi: 10.1097/00000421-198208000-00005. [DOI] [PubMed] [Google Scholar]
  2. Ang P. T., Buzdar A. U., Smith T. L., Kau S., Hortobagyi G. N. Analysis of dose intensity in doxorubicin-containing adjuvant chemotherapy in stage II and III breast carcinoma. J Clin Oncol. 1989 Nov;7(11):1677–1684. doi: 10.1200/JCO.1989.7.11.1677. [DOI] [PubMed] [Google Scholar]
  3. Bonadonna G., Valagussa P. Dose-response effect of adjuvant chemotherapy in breast cancer. N Engl J Med. 1981 Jan 1;304(1):10–15. doi: 10.1056/NEJM198101013040103. [DOI] [PubMed] [Google Scholar]
  4. Colleoni M., Price K., Castiglione-Gertsch M., Goldhirsch A., Coates A., Lindtner J., Collins J., Gelber R. D., Thürlimann B., Rudenstam C. M. Dose-response effect of adjuvant cyclophosphamide, methotrexate, 5-fluorouracil (CMF) in node-positive breast cancer. International Breast Cancer Study Group. Eur J Cancer. 1998 Oct;34(11):1693–1700. doi: 10.1016/s0959-8049(98)00209-3. [DOI] [PubMed] [Google Scholar]
  5. Fisher B., Anderson S., Wickerham D. L., DeCillis A., Dimitrov N., Mamounas E., Wolmark N., Pugh R., Atkins J. N., Meyers F. J. 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. 1997 May;15(5):1858–1869. doi: 10.1200/JCO.1997.15.5.1858. [DOI] [PubMed] [Google Scholar]
  6. Fumoleau P., Devaux Y., Vo Van M. L., Kerbrat P., Fargeot P., Schraub S., Mihura J., Namer M., Mercier M. Premenopausal patients with node-positive resectable breast cancer. Preliminary results of a randomised trial comparing 3 adjuvant regimens: FEC 50 x 6 cycles vs FEC 50 x 3 cycles vs FEC 75 x 3 cycles. The French Adjuvant Study Group. Drugs. 1993;45 (Suppl 2):38–45. doi: 10.2165/00003495-199300452-00007. [DOI] [PubMed] [Google Scholar]
  7. Glucksberg H., Rivkin S. E., Rasmussen S., Tranum B., Gad-el-Mawla N., Costanzi J., Hoogstraten B., Athens J., Maloney T., McCracken J. Combination chemotherapy (CMFVP) versus L-phenylalanine mustard (L-PAM) for operable breast cancer with positive axillary nodes: a Southwest Oncology Group Study. Cancer. 1982 Aug 1;50(3):423–434. doi: 10.1002/1097-0142(19820801)50:3<423::aid-cncr2820500307>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  8. Howell A., Rubens R. D., Bush H., George W. D., Howat J. M., Crowther D., Sellwood R. A., Hayward J. L., Knight R. K., Bulbrook R. D. A controlled trial of adjuvant chemotherapy with melphalan versus cyclophosphamide, methotrexate, and fluorouracil for breast cancer. Recent Results Cancer Res. 1984;96:74–89. doi: 10.1007/978-3-642-82357-2_10. [DOI] [PubMed] [Google Scholar]
  9. Longo D. L., Duffey P. L., DeVita V. T., Jr, Wesley M. N., Hubbard S. M., Young R. C. The calculation of actual or received dose intensity: a comparison of published methods. J Clin Oncol. 1991 Nov;9(11):2042–2051. doi: 10.1200/JCO.1991.9.11.2042. [DOI] [PubMed] [Google Scholar]
  10. Mouridsen H. T., Rose C., Brincker H., Thorpe S. M., Rank F., Fischerman K., Andersen K. W. 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. 1984;96:117–128. doi: 10.1007/978-3-642-82357-2_14. [DOI] [PubMed] [Google Scholar]
  11. Peto R., Pike M. C., Armitage P., Breslow N. E., Cox D. R., Howard S. V., Mantel N., McPherson K., Peto J., Smith P. G. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. Br J Cancer. 1977 Jan;35(1):1–39. doi: 10.1038/bjc.1977.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pronzato P., Campora E., Amoroso D., Bertelli G., Botto F., Conte P. F., Sertoli M. R., Rosso R. Impact of administration-related factors on outcome of adjuvant chemotherapy for primary breast cancer. Am J Clin Oncol. 1989 Dec;12(6):481–485. doi: 10.1097/00000421-198912000-00004. [DOI] [PubMed] [Google Scholar]
  13. Redmond C., Fisher B., Wieand H. S. The methodologic dilemma in retrospectively correlating the amount of chemotherapy received in adjuvant therapy protocols with disease-free survival. Cancer Treat Rep. 1983 Jun;67(6):519–526. [PubMed] [Google Scholar]
  14. Rodriguez-Kraul R., Hortobagyi G. N., Buzdar A. U., Blumenschein G. R. Combination chemotherapy for breast cancer metastatic to bone marrow. Cancer. 1981 Jul 15;48(2):227–232. doi: 10.1002/1097-0142(19810715)48:2<227::aid-cncr2820480203>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  15. Saarto T., Blomqvist C., Rissanen P., Auvinen A., Elomaa I. Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer. Br J Cancer. 1997;75(2):301–305. doi: 10.1038/bjc.1997.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Senn H. J., Jungi W. F., Amgwerd R., Hochuli E., Ammann J., Engelhart G., Heinz C., Wick A., Enderlin F., Creux G. Adjuvant chemoimmunotherapy with LMF + BCG in node-negative and node-positive breast cancer: 8 year results. Recent Results Cancer Res. 1984;96:90–101. doi: 10.1007/978-3-642-82357-2_11. [DOI] [PubMed] [Google Scholar]
  17. Tormey D., Gelman R., Falkson G. Prospective evaluation of rotating chemotherapy in advanced breast cancer. An Eastern Cooperative Oncology Group Trial. Am J Clin Oncol. 1983 Feb;6(1):1–18. [PubMed] [Google Scholar]
  18. 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. Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. N Engl J Med. 1994 May 5;330(18):1253–1259. doi: 10.1056/NEJM199405053301801. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES