Senologie - Zeitschrift für Mammadiagnostik und -therapie 2012; 9 - A160
DOI: 10.1055/s-0032-1313526

Bisphosphonates may improve survival of breast cancer patients with disseminated tumor cells in bone marrow

EF Solomayer 1, M Banys 2, 3, G Gebauer 3, N Krawczyk 2, D Wallwiener 2, P Hirnle 5, W Janni 4, HJ Lück 6, S Becker 2, J Huober 7, B Wackwitz 8, T Fehm 2
  • 1Klinik für Frauenheilkunde, Geburtshilfe und Reproduktionsmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar
  • 2Universitäts-Frauenklinik Tübingen, Universität Tübingen, Tübingen
  • 3Frauenklinik, Marienkrankenhaus Hamburg, Hamburg
  • 4Universitäts-Frauenklinik, Universitätsklinikum Düsseldorf, Düsseldorf
  • 5Klinik für Strahlentherapie, Klinikum Bielefeld, Bielefeld
  • 6Gynäkologisch-Onkologischen Schwerpunktpraxis, Hannover
  • 7Brustkrebszentrum, Kantonsspital St. Gallen, St. Gallen, Switzerland
  • 8Norvartis Oncology, Nürnberg

Introduction:

The presence of disseminated tumor cells (DTC) in bone marrow (BM) is an independent prognostic factor in breast cancer. In addition, tumor cells are able to survive chemotherapy and their persistence is strongly associated with poor outcome. Bisphosphonates have been previously reported to improve survival in nonmetastatic breast cancer. The purpose of this study was to investigate the impact of zoledronic acid (ZOL) on DTC persistence and patients' survival.

Material and methods:

In total, 96 DTC positive breast cancer patients were included into this prospective open-label parallel-group study between 2002 – 2004. Patients were randomized 1:1 to adjuvant therapy alone (control) or with intravenous ZOL q4w for 24 months. In 71 and 59 cases an additional BM biopsy was conducted 12 months and 24 months after diagnosis, respectively.

Results:

An adequate follow-up of at least 8 months was available for 86 patients (ZOL group: 40 pts, controls: 46 pts; median follow-up 88 months, range: 8–108 mths). Patients in the control group were more likely to die than those in ZOL group (11% vs. 2%, p=0.106). In addition 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). These differences did not reach statistic significance due to small sample size. However, a trend toward shorter overall and disease-free survival in the control group was observed. Patients treated with ZOL became DTC negative after 24 months of treatment. DTC persistence was associated with shorter overall survival (p=0.011).

Discussion:

Intravenous zoledronic acid may help to eradicate DTC from bone marrow. Our data support the possible protective effect of bisphosphonates in DTC positive patients.