Persistence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients predicts increased risk for relapse—Results of pooled European data

Abstract

10083 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. 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 697 patients from academic breast cancer units in Oslo (n=356), Munich (n=228) and Tuebingen (n=113) during recurrence-free follow-up at a median interval of 32.4 months (standard deviation [std] 19.4 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, Tuebingen), or AE1 and AE3 (Oslo), directed against cytokeratin (CK). Patients were followed for a median of 54.2 months (std 24.5 mon) after primary diagnosis. Results: Persistent DTC in the BM were detected in 15.6% of the patients (n=109). The Kaplan-Meier estimate for mean distant relapse-free survival estimate was 155.6 mon (142.4 - 168.9 95%CI) in patients with negative and 102.3 mon (93.6 - 111.0, 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 (164.4 [155.6 - 173.3]), than patients with positive BM status (101.7 mon [89.4 - 113.9], p< .0001). In multivariate Cox regression analysis, allowing for bone marrow status, tumor size, nodal status, histopathological grading and hormone receptor status, DTC was of higher independent prognostic significance for subsequent reduced breast cancer specific survival (RR 5.9, 2.8 - 12.8, 95% CI, p< .0001), than nodal status at time of primary diagnosis (RR 1.2, 1.0 - 1.3, 95% CI, p=.014). 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. No significant financial relationships to disclose.