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Breast Cancer Research and Treatment

, Volume 144, Issue 1, pp 113–121 | Cite as

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. Fox
  • Alberto Bottini
  • Daniele Generali
Clinical trial

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.

Keywords

Zoledronic acid Breast cancer Circulating tumor cells Ki67 Window therapy 

Notes

Acknowledgments

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

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Chiara Foroni
    • 1
  • Manuela Milan
    • 1
  • Carla Strina
    • 1
  • Mariarosa Cappelletti
    • 1
  • Claudia Fumarola
    • 4
  • Mara Bonelli
    • 4
  • Ramona Bertoni
    • 3
  • Giuseppina Ferrero
    • 3
  • Mara Maldotti
    • 1
  • Elena Takano
    • 7
  • Daniele Andreis
    • 1
  • Sergio Venturini
    • 2
  • Giulia Brugnoli
    • 1
  • Pier Giorgio Petronini
    • 4
  • Vanessa Zanoni
    • 1
  • Laura Pritzker
    • 5
  • Kenneth Pritzker
    • 5
  • Amadeo Parissenti
    • 8
  • Daniele Santini
    • 6
  • Stephen B. Fox
    • 7
  • Alberto Bottini
    • 1
  • Daniele Generali
    • 1
  1. 1.U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e FarmacogenomicaA.O. Istituti Ospitalieri di CremonaCremonaItaly
  2. 2.CE.R.G.A.S., Università BocconiMilanItaly
  3. 3.U.O. Anatomia PatologicaA.O. Istituti Ospitalieri di CremonaCremonaItaly
  4. 4.Dipartimento di Medicina SperimentaleParmaItaly
  5. 5.Rna Diagnostics IncTorontoCanada
  6. 6.Oncologia MedicaUniversity Campus Bio-Medico RomaRomeItaly
  7. 7.Peter MacCallum Cancer Centre and University of MelbourneMelbourneAustralia
  8. 8.Laurentian UniversitySudburyCanada

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