Effect of zoledronate on persisting isolated tumor cells (ITC) in the bone marrow (BM) of patients without recurrence of early breast cancer

Abstract

9515 Background: Patients with persisting ITC in the BM after primary therapy show an increased risk for distant relapse and shortened survival (Janni et al., Cancer 2001; Wiedswang et al., SABCS 2003). Adjuvant chemotherapy, however, seems to have only limited effect on ITC in dormant state (Braun et al., 2000). Aim of this study was to investigate the therapeutic efficacy of zoledronate on the persistence of ITC in BM after completion of primary therapy. Methods: Zoledronate was applied at 4 mg q4wx6mon (loading dose 8mg) to 14 breast cancer patients with persisting ITC in the BM. Patients were to have completed surgery, leading to R0 resection and adjuvant chemotherapy for at least 6 months and had no evidence for recurrence at this point of time. In a matched pair analysis, these patients were compared to 14 patients with persisting ITC in the BM, who received no further therapy. The BM was re-examined after a median of 8 months (range 6.5–9.83) in the treatment group and 9 months (range 2.33–29.17) in the control group. ITC were detected by immunocytochemical staining using the pan-cytokeratin antibody A45-B/B3 and the APAAP technique. Results: Primary tumor characteristics, i.e. tumor size (P=.66), axillary nodal status (P=1.0) and histopathological grading (P=.76), as well as surgical (P=.23), adjuvant systemic (P=.10) and irradiation treatment (P=.36) were well balanced between both patient groups. While ITC were detected in all 28 patients at the time of first BM aspiration, no patient showed ITC in the BM following 6 months of zoledronate therapy. In contrast, persisting ITC were detected in 4 patients (29%) of the control group without treatment (P=.03). Conclusions: These preliminary results indicate potential antineoplastic effect of the cell-cycle independent agent zoledronate on persisting ITC in dormant state. In our view, these data provide a hypothesis generating basis to investigate the therapeutic efficacy of zoledronate on ITC in a secondary adjuvant setting by prospectively randomised trials. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis