P5-18-07: Presence of Disseminated Tumor Cells after Adjuvant Chemotherapy in Breast Cancer and Disseminated Tumor Cells Monitoring during Secondary Adjuvant Treatment.
Authors: Synnestvedt M , Borgen E , Wist E , Wiedswang G , Weyde K , Risberg T , Kersten C , Mjaaland I , Vindi L , Schirmer CB , Nesland JM , Naume B 
Published: June 2012

Introduction: Detection of disseminated tumor cells (DTC) after completion of systemic adjuvant treatment is a strong predictor of early systemic relapse and death. This analysis can discover early failure of a chosen adjuvant systemic treatment. In this study, we wanted to evaluate the value of DTC detection in bone marrow (BM) as a surrogate marker for response to docetaxel rescue treatment, to predict the effect of this treatment. Further, we wanted to compare disease free survival between patients treated with docetaxel resulting in eradication of DTC after treatment and patients treated with docetaxel where DTC persists after treatment. The follow up of the study is still ongoing. Here, we present the preliminary descriptive data from the study.

Materials and Methods: A total of 1128 pts with node positive or high risk node negative disease (T1c/T2GII-IIIN0) was enrolled in the period from October 2003 to May 2008. All patients had completed primary surgery and received 6 cycles of adjuvant antracycline containing chemotherapy. The first BM aspiration was performed 8–12 weeks after termination of adjuvant chemotherapy (BM1). A second BM aspiration was performed 6 months later (BM2). The processing of BM and DTC analysis (by ICC) were performed as previsously described (Wiedswang G et al, J Clin Oncol 2003). If BM2 was positive (+) for DTC, the patient was treated with docetaxel (3qw, 6 courses) Docetaxel-treated patients were reexamined at the inclusion hospital with new BM analysis at approximately 1 month (BM3) and 13 months (BM4) after the last docetaxel infusion.

Results: Of 997 patients with conclusive DTC results for both BM1 and BM2, 83 patients (8.3%) were BM1 positive and 78 (7.8%) BM2 positive. Among the BM1+ patients, 15 (18.1%) were BM2+. The concordance between BM1 and BM2 were 87%. Of the patients positive at one or both time points, the concordance was 10% (15/146). The BM1 was not significantly associated with primary tumor characteristics (although borderline significance for Grade and ER status), whereas for BM2, DTC+ patients had increased frequency of node positive disease and pN2-3 stage (p=0.001, chi-square), and were positively associated with lobular carcinoma (p=0.01, chi-square). At BM1 24.7% of the DTC+ patients had &gt;1 DTC, and 9.9% had ≥3 DTC. For BM2, 48.2% had &gt;1 DTC, and 25.7% had ≥3 DTC. For patients with positive BM2 receiving docetaxel, the BM3 turned DTC negative in 55 of 66 evaluable cases (83.3%), and 48 of 59 were negative in BM4 (81.4%). Of 67 patients with a conclusive BM result at either BM3 or BM4, 12 were BM positive. Of 16 patients with ≥3 DTC before docetaxel treatment, only 4 patients were positive after treatment (25%).

Conclusions: DTC status after adjuvant antracycline containing chemotherapy changes during the first 9 months of FU, with increased DTC positivity among patients with pN+ disease and lobular carcinomas. After docetaxel rescue treatment, the majority of patients experience disappearance of the DTCs. The clinical significance of these results awaits mature FU data, but the present results may indicate possibility for eradication of residual disease by alternative chemotherapy.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-07.