Background: Recent data suggest that circulating tumor cells (CTCs) are of prognostic relevance in early as well as metastatic breast cancer. However, there is a lack of data on the prognostic impact of CTCs to predict late recurrences during long-term follow-up, especially in patients with hormone receptor positive tumors. Methods: The SUCCESS A trial is a randomized Phase III study, in which patients with high-risk early breast cancer were first randomized to 3 cycles of epirubicin-fluorouracil-cyclophosphamide followed by either 3 cycles of docetaxel or 3 cycles of gemcitabine-docetaxel, followed by a second randomization to 2 vs. 5 years of zoledronate treatment. Presence of CTCs 5 years after chemotherapy was assessed using the CellSearch System (Janssen Diagnostics, LLC), and CTC positivity was defined as ≥ 1 CTC in 7.5 ml whole blood. Recurrence-free survival (RFS) was analyzed by univariable and multivariable Cox regressions. Survival time was measured as of the date of blood sampling for CTC assessment. Results: Follow-up data for patients with known CTC status 5 years after chemotherapy were available for 206 (5.5%) of 3754 randomized patients (median time interval of CTC assessment 62.4 months since randomization). The CTC status was positive in 16 (7.8%) patients (range 1 – 53 CTCs). Median follow-up time after CTC assessment was 360 days (range 1 – 911 days). Overall, 13 late recurrences were observed; 11 in 153 hormone receptor positive patients and 2 in 53 hormone receptor negative patients. In hormone receptor positive patients, CTC status was a significant prognostic factor for RFS in univariable (hazard ratio [HR] 5.14, 95% confidence interval [CI] 1.47 – 18.03, p = 0.011) and in multivariable cox regressions adjusted for age, tumor stage, nodal stage, grade, histological type, and HER2 status (HR 5.95, 95%CI 1.14 – 31.16, p = 0.035). Conclusions: The presence of CTCs 5 years after chemotherapy was associated with decreased RFS, suggesting that persisting CTCs during long term follow-up independently predict late recurrences in hormone receptor positive patients. Extended follow-up data will be presented at the meeting. Clinical trial information: NCT02181101