The study investigated the anti-tumour effect of zoledronic acid (ZA) administered alone in a biological windowtherapyinna ̈ıvebone-onlymetastaticandlocally advanced breast cancer (LABC) patients. 33 patients with LABC (Group 1) and 20 patients with a first diagnosis of bone metastasis only (Group 2) received 4 mg single dose of ZA, 14 days (biological window) before starting any treat- ment. In Group 1, Ki67, CD34, p53/bcl-2 and caspase 3 expression along with the adenosine triphosphate (ATP) levels and RNA disruption index were evaluated as markers of tumor growth in tumour specimens obtained before and after ZA administration (basal, day 14). In Group 2, the total enumeration of circulating tumour cells (CTCs), and of M30?ve CTCs along with the soluble marker of cell death (M30/M65) were carried-out as markers of tumor dissemi- nation at baseline, at 48 h and day 14th. In Group 1, there was a significant reduction in Ki67, CD34, bcl-2 expression after 14 days ZA based-treatment (p = 0.0032; p = 0.0001, p 0.00001 respectively). ZA showed a significant increase of RNA disruption (p 0.0076). In Group 2, we observed a significant reduction of CTCs number after 48h (p = 0.0012), followed by a significant rebound at 14 days (p = 0.012). The apoptotic CTCs/M30?ve and M65 levels significantly increased under treatment (p = 0.018 and p = 0.039 respectively) after drug administration when compared to the baseline. These results are the first pro- spective in vivo data showing the direct pure anti-tumour effect (either on the tumour cell or on CTCs) of ZA.

Pure anti-tumor effect of zoledronic acid in naïve bone-only metastatic and locally advanced breast cancer: proof from the "biological window therapy"

Maldotti, Mara;VENTURINI, SERGIO;
2014-01-01

Abstract

The study investigated the anti-tumour effect of zoledronic acid (ZA) administered alone in a biological windowtherapyinna ̈ıvebone-onlymetastaticandlocally advanced breast cancer (LABC) patients. 33 patients with LABC (Group 1) and 20 patients with a first diagnosis of bone metastasis only (Group 2) received 4 mg single dose of ZA, 14 days (biological window) before starting any treat- ment. In Group 1, Ki67, CD34, p53/bcl-2 and caspase 3 expression along with the adenosine triphosphate (ATP) levels and RNA disruption index were evaluated as markers of tumor growth in tumour specimens obtained before and after ZA administration (basal, day 14). In Group 2, the total enumeration of circulating tumour cells (CTCs), and of M30?ve CTCs along with the soluble marker of cell death (M30/M65) were carried-out as markers of tumor dissemi- nation at baseline, at 48 h and day 14th. In Group 1, there was a significant reduction in Ki67, CD34, bcl-2 expression after 14 days ZA based-treatment (p = 0.0032; p = 0.0001, p 0.00001 respectively). ZA showed a significant increase of RNA disruption (p 0.0076). In Group 2, we observed a significant reduction of CTCs number after 48h (p = 0.0012), followed by a significant rebound at 14 days (p = 0.012). The apoptotic CTCs/M30?ve and M65 levels significantly increased under treatment (p = 0.018 and p = 0.039 respectively) after drug administration when compared to the baseline. These results are the first pro- spective in vivo data showing the direct pure anti-tumour effect (either on the tumour cell or on CTCs) of ZA.
2014
144
1
113
121
http://dx.doi.org/10.1007/s10549-014-2840-y
BREAST CANCER; CIRCULATING TUMOR CELLS; KI67; WINDOW THERAPY; ZOLEDRONIC ACID; ADULT; AGED; AGED; 80 AND OVER; BONE DENSITY CONSERVATION AGENTS; BONE NEOPLASMS; BREAST NEOPLASMS; DIPHOSPHONATES; FEMALE; HUMANS; IMIDAZOLES; IMMUNOHISTOCHEMISTRY; MIDDLE AGED; NEOPLASTIC CELLS; CIRCULATING; ONCOLOGY; CANCER RESEARCH
Foroni, Chiara; Milan, Manuela; Strina, Carla; Cappelletti, Mariarosa; Fumarola, Claudia; Bonelli, Mara; Bertoni, Ramona; Ferrero, Giuseppina; Maldott...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1715135
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