Artikel
Persistence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients predicts increased risk for relapse – results of pooled European data
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Veröffentlicht: | 20. März 2006 |
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Background: The prognostic significance of DTC in the BM of breast cancer patients at the time of primary diagnosis has recently been confirmed by a large pooled analysis (Figure 1 [Fig. 1]). If the persistence of DTC after adjuvant therapy confers a similar risk for relapse, there might be an indication for secondary adjuvant treatment.
Methods: We analyzed BM aspirates of 584 patients from academic breast cancer units in Oslo (n=356) and Munich (n=228) during recurrence-free follow-up at a median interval of 38.6 months (standard deviation [std] 18.9 mon) after primary diagnosis of breast cancer pT1-4, pN0-3 pM0. Carcinoma cells were detected using a standardized immunoassay with the monoclonal antibodies A45-B/B3 (Munich) or AE1 and AE3 (Oslo), directed against cytokeratin (CK). Patients were followed for a median of 62.7 months (std 23.1 mon) after primary diagnosis.
Results: Persistent DTC in the BM were detected in 14.0% of the patients (n=82). The Kaplan-Meier estimate for mean relapse-free survival was 159.0 mon (153.2 – 164.7 95% CI) in patients with negative and 91.5 mon (74.4 – 108.6, 95% CI, p< .0001, log rank test) in patients with positive BM status. Patients without evidence of persistent DTC had a significantly longer overall survival (165.5 [156.7 – 174.4]), than patients with positive BM status (104.0 mon [91.5 – 116.5], p< .0001). In multivariate Cox regression analysis, allowing for bone marrow status, tumor size and nodal status, DTC was an independent significant predictor for reduced breast cancer specific survival (RR 5.1, p< .0001).
Conclusion: Evidence of persistent DTC in breast cancer patients indicates an increased risk for subsequent relapse, and may serve for monitoring in future clinical trials. Such trials might investigate the benefit of individualized secondary adjuvant treatment or extended adjuvant therapy of patients with DTC.