Effect of zoledronate on persisting isolated tumour cells in patients with early breast cancer.
BACKGROUND
There is strong evidence for the isolated tumour cells (ITCs) in the bone marrow of breast cancer patients having prognostic impact both at primary diagnosis and during recurrence-free follow-up. The goal of this study was to investigate the therapeutic efficacy of zoledronate on the persistence of ITC.


METHODS
A total of 172 primary breast cancer patients without evidence of distant recurrence but detection of ITC in bone marrow were followed up. Zoledronate was administered every 4 weeks for 6 months to 31 patients who had completed surgery and adjuvant chemotherapy. In a matched-pair analysis, these patients were compared to 141 patients who did not receive additional zoledronate treatment. The bone marrow was re-examined after a median of 7.9 months (SD 0.89) and 11.5 months (SD 12.41; p=0.11), respectively. Patients were followed-up prospectively for a median of 39 months after the first aspiration.


RESULTS
While ITCs were detected in all 172 patients at the time of first bone marrow aspiration, ITCs were detected in four patients (13%) following 6 months of zoledronate therapy in contrast to 38 patients (27%) of the control group (p=0.099). The reduction in cell numbers between the first and second aspiration reached statistical significance in the zoledronate group (p=0.02 vs. p=0.14). Persistent ITCs at the follow-up aspiration were associated with reduced recurrence-free survival (p=0.05).


CONCLUSIONS
These results indicate a potential antineoplastic effect of the cell cycle-independent agent zoledronate on persisting ITCs in a dormant state.
Rack
Brigitte
B
Department of Gynecology and Obstetrics, Klinik und Poliklinik fuer Frauenheilkunde und Geburtshilfe, Campus Innenstadt, Ludwig-Maximilians-Universitaet, Muenchen, Germany. brigitte.rack@med.uni-muenchen.de
Jückstock
Julia
J
Genss
Eva-Maria
EM
Schoberth
Alexandra
A
Schindlbeck
Christian
C
Strobl
Barbara
B
Heinrigs
Maja
M
Rammel
Gerhard
G
Zwingers
Thomas
T
Sommer
Harald
H
Friese
Klaus
K
Janni
Wolfgang
W
D000328:Adult; D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002453:Cell Cycle; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008875:Middle Aged; D015233:Models, Statistical; D012008:Recurrence; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid