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

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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.

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Acknowledgments

This study was partly funded by Associazione Ricerca in Campo Oncologico Onlus, Cremona, Italy

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Authors and Affiliations

  1. U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100, Cremona, Italy

    Chiara Foroni, Manuela Milan, Carla Strina, Mariarosa Cappelletti, Mara Maldotti, Daniele Andreis, Giulia Brugnoli, Vanessa Zanoni, Alberto Bottini & Daniele Generali

  2. CE.R.G.A.S., Università Bocconi, Via Roentgen 1, 26100, Milan, Italy

    Sergio Venturini

  3. U.O. Anatomia Patologica, A.O. Istituti Ospitalieri di Cremona, Viale Concordia 1, Cremona, Italy

    Ramona Bertoni & Giuseppina Ferrero

  4. Dipartimento di Medicina Sperimentale, Via Volturno 39, 43125, Parma, Italy

    Claudia Fumarola, Mara Bonelli & Pier Giorgio Petronini

  5. Rna Diagnostics Inc, Toronto, ON, Canada

    Laura Pritzker & Kenneth Pritzker

  6. Oncologia Medica, University Campus Bio-Medico Roma, Rome, Italy

    Daniele Santini

  7. Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC, Australia

    Elena Takano & Stephen B. Fox

  8. Laurentian University, Sudbury, ON, Canada

    Amadeo Parissenti

Authors
  1. Chiara Foroni
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  2. Manuela Milan
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  3. Carla Strina
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  4. Mariarosa Cappelletti
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  5. Claudia Fumarola
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  9. Mara Maldotti
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  10. Elena Takano
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  13. Giulia Brugnoli
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  15. Vanessa Zanoni
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  16. Laura Pritzker
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  18. Amadeo Parissenti
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  19. Daniele Santini
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  20. Stephen B. Fox
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  21. Alberto Bottini
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  22. Daniele Generali
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Correspondence to Daniele Generali.

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Foroni, C., Milan, M., Strina, C. et al. 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 Res Treat 144, 113–121 (2014). https://doi.org/10.1007/s10549-014-2840-y

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  • DOI: https://doi.org/10.1007/s10549-014-2840-y

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