Persistence of isolated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse – a European pooled analysis

Abstract #304 Purpose: The prognostic significance of DTC in the BM of breast cancer pts at the time of primary diagnosis has already been confirmed by a large pooled analysis. In view of the lack of early indicators for secondary adjuvant treatment, we here evaluated whether the persistence of DTC after adjuvant therapy confers a risk for relapse and breast cancer-related death. Patients and Methods: We analyzed BM aspirates of 723 pts from academic breast cancer units in Oslo (n=356), Munich (n=228) and Tuebingen (n=139) during recurrence-free follow-up at a mean interval of 31.7 months (standard deviation [std] 19.4 months) 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). Pts were followed for a median of 54.5 months (SD 25.1 months) after primary diagnosis. Results: Persistent DTC in the BM was detected in 15.5% of the pts (n=112). The Kaplan-Meier estimate for mean distant relapse-free survival was 162.5 months (157.9 – 167.0 95%CI) in pts with negative and 102.4 months (94.2 – 110.6, 95% CI, p< .0001, log rank test) in pts with positive BM status. The mean overall survival was 170.1 months, (167.7 – 172.5 95% CI), compared to 113.4 months in patients with persistent DTC in BM (107.3 – 119.5, p < .0001). In multivariate Cox regression analysis, allowing for BM status, tumor size, nodal status and histopathological grading, presence of DTC was an independent prognostic factor for reduced breast cancer specific survival ((RR 3.42, 1.64 – 7.13 95% CI, p= .001). Conclusion: Persistent DTC significantly predicts an increased risk for subsequent relapse, and, therefore, might serve as a potent monitoring tool for the follow-up of breast cancer pts. Future therapeutic intervention trials are currently being initiated to assess the benefit of secondary adjuvant treatment based on DTC detection as stratification parameter. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 304.