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

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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.