559 Background: DTC in BM is associated with an increased risk of distant recurrence (DR) and death in patients (pts) with ESBC, particularly when these cells are detected after adjuvant therapy. Bisphosphonates can act as antitumor agents by various mechanisms including induction of tumor cell apoptosis. Clodronate in pts with DTC at BC diagnosis reduced the incidence of metastases and improved survival. ZA is significantly more potent than clodronate in inhibiting bone resorption. We designed a pilot study to evaluate ZA in pts with ESBC with DTC. Decrease in DTC could serve as a surrogate marker of antitumor effect. Methods: DTCs are detected by immunomagnetic enrichment + flow cytometry (FC): BM is enriched with anti-EpCAM-conjugated iron particles, DTC are detected with EpCAM, CD45, and nucleic acid content. Pts with stage I-III BC are evaluated for DTC with a unilateral BM aspiration following neoadjuvant or adjuvant CTX; eligibility was defined as >4 DTC/ml, which is 2.5 SD > than 50 normal BM (Par...