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

Chiara Foroni, Manuela Milan, Carla Strina, Mariarosa Cappelletti, Claudia Fumarola, Mara Bonelli, Ramona Bertoni, Giuseppina Ferrero, Mara Maldotti, Elena Takano, Daniele Andreis, Sergio Venturini, Giulia Brugnoli, Pier Giorgio Petronini, Vanessa Zanoni, Laura Pritzker, Kenneth Pritzker, Amadeo Parissenti, Daniele Santini, Stephen B. FoxAlberto Bottini, Daniele Generali

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Abstract

The study investigated the anti-tumour effect of zoledronic acid (ZA) administered alone in a biological window therapy in naïve bone-only metastatic and locally 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 treatment. 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 dissemination 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 48 h (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 prospective in vivo data showing the direct pure anti-tumour effect (either on the tumour cell or on CTCs) of ZA.

Original languageEnglish
Pages (from-to)113-121
Number of pages9
JournalBreast Cancer Research and Treatment
Volume144
Issue number1
DOIs
Publication statusPublished - 2014

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Keywords

  • Breast cancer
  • Circulating tumor cells
  • Ki67
  • Window therapy
  • Zoledronic acid

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Foroni, C., Milan, M., Strina, C., Cappelletti, M., Fumarola, C., Bonelli, M., Bertoni, R., Ferrero, G., Maldotti, M., Takano, E., Andreis, D., Venturini, S., Brugnoli, G., Petronini, P. G., Zanoni, V., Pritzker, L., Pritzker, K., Parissenti, A., Santini, D., ... Generali, D. (2014). Pure anti-tumor effect of zoledronic acid in naïve bone-only metastatic and locally advanced breast cancer: Proof from the "biological window therapy". Breast Cancer Research and Treatment, 144(1), 113-121. https://doi.org/10.1007/s10549-014-2840-y