Influence of zoledronic acid on disseminated tumor cells in bone marrow and survival: results of a prospective clinical trial

• Published in: Senologie - Zeitschrift für Mammadiagnostik und -therapie
• Main Authors: Banys, M, Solomayer, E, Gebauer, G, Janni, W, Lueck, H, Becker, S, Huober, J, Krämer, B, Wackwitz, B, Hirnle, P, Wallwiener, D, Fehm, T
• Format: Conference Proceeding
• Language: English
• Published: 04.06.2013
• ISSN: 1611-6453; 1611-647X
• DOI: 10.1055/s-0033-1347542

Introduction: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients is associated with reduced clinical outcome. Bisphosphonate treatment was shown to eradicate DTC. This controlled study aimed to investigate the influence of zoledronic acid (ZOL) on DTC and survival of breast cancer patients. Methods: Patients with primary breast cancer and DTC-positive bone marrow were randomized to treatment with ZOL plus adjuvant systemic therapy (n = 40) or adjuvant systemic therapy alone (n = 46). DTC were identified by immunocytochemistry using the antibody A45B/B3. The change in DTC numbers at 12 months and 24 months versus baseline, as well as patient outcomes were evaluated. Results: 86 patients were included into survival analysis (median follow-up: 88 months, range: 8 – 108 mths). Patients in the control group were more likely to die during follow-up than those in the ZOL-group (11% vs. 2%, p = 0.106). 15% of patients in the control group presented with relapse whereas only 8% of ZOL group patients developed metastatic or recurrent disease during follow-up (p = 0.205). At 24 months, 16% of patients from the control group were still DTC positive, whereas all patients treated with ZOL became DTC negative (p = 0.032). Patients presenting with persistent DTC 12 months after diagnosis had significantly shorter overall survival (p = 0.011). Conclusions: Bisphosphonates contribute to eradication of disseminated tumor cells. The positive influence of bisphosphonates on survival in the adjuvant setting may be due to their effects on DTC.