Bisphosphonates as anticancer agents in early breast cancer: preclinical and clinical evidence

doi:10.1186/s13058-015-0634-8

Review

. 2015 Sep 2;17(1):121.

doi: 10.1186/s13058-015-0634-8.

Bisphosphonates as anticancer agents in early breast cancer: preclinical and clinical evidence

Affiliations

¹ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. d.santini@unicampus.it.
² Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. l.stumbo@unicampus.it.
³ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. c.spoto@unicampus.it.
⁴ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. l.donofrio@unicampus.it.
⁵ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. f.pantano@unicampus.it.
⁶ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. m.iuliani@unicampus.it.
⁷ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. m.fioramonti@unicampus.it.
⁸ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. a.zoccoli@unicampus.it.
⁹ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. g.ribelli@unicampus.it.
¹⁰ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. v.virzi@unicampus.it.
¹¹ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. b.vincenzi@unicampus.it.
¹² Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. g.tonini@unicampus.it.

PMID: 26328589
PMCID: PMC4557314
DOI: 10.1186/s13058-015-0634-8

Review

Bisphosphonates as anticancer agents in early breast cancer: preclinical and clinical evidence

Daniele Santini et al. Breast Cancer Res. 2015.

. 2015 Sep 2;17(1):121.

doi: 10.1186/s13058-015-0634-8.

Authors

Affiliations

¹ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. d.santini@unicampus.it.
² Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. l.stumbo@unicampus.it.
³ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. c.spoto@unicampus.it.
⁴ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. l.donofrio@unicampus.it.
⁵ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. f.pantano@unicampus.it.
⁶ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. m.iuliani@unicampus.it.
⁷ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. m.fioramonti@unicampus.it.
⁸ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. a.zoccoli@unicampus.it.
⁹ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. g.ribelli@unicampus.it.
¹⁰ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. v.virzi@unicampus.it.
¹¹ Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. b.vincenzi@unicampus.it.
¹² Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. g.tonini@unicampus.it.

PMID: 26328589
PMCID: PMC4557314
DOI: 10.1186/s13058-015-0634-8

Abstract

Bisphosphonates (BPs) are approved as standard therapy in breast cancer for the treatment of bone metastases, since they were demonstrated to reduce the prevalence of skeletal-related events including fractures and hypercalcemia. In the adjuvant setting, BPs can be given to prevent and treat tumor therapy-induced bone loss in premenopausal and postmenopausal women and, owing to their beneficial effect on bone turnover, have also been evaluated for prevention of bone metastases occurrence. In this article we will review the mechanisms through which BPs have been demonstrated to prevent premetastatic niche formation and cell proliferation in bone lesions. Moreover, preclinical evidence of antitumoral effects of BPs will be presented and results from the most important clinical trials will be described critically. BPs may clearly play a clinically important role in early breast cancer in a postmenopausal adjuvant setting.

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References

1. Coleman RE. Skeletal complications of malignancy. Cancer. 1997;80:1588–94. doi: 10.1002/(SICI)1097-0142(19971015)80:8+<1588::AID-CNCR9>3.0.CO;2-G. - DOI - PubMed
1. Rogers MJ, Gordon S, Benford HL, et al. Cellular and molecular mechanisms of action of bisphosphonates. Cancer. 2000;88:2961–78. doi: 10.1002/1097-0142(20000615)88:12+<2961::AID-CNCR12>3.0.CO;2-L. - DOI - PubMed
1. Kuo YC, Su CH, Liu CY, Chen TH, Chen CP, Wang HS. Transforming growth factor-beta induces CD44 cleavage that promotes migration of MDA-MB-435s cells through the up-regulation of membrane type 1-matrix metalloproteinase. Int J Cancer. 2009;124:2568–76. doi: 10.1002/ijc.24263. - DOI - PubMed
1. Martínez AS, Huelsken J. The niche under siege: novel targets for metastasis therapy. J Intern Med. 2013;274:127–36. doi: 10.1111/joim.12024. - DOI - PubMed
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[1] Coleman RE. Skeletal complications of malignancy. Cancer. 1997;80:1588–94. doi: 10.1002/(SICI)1097-0142(19971015)80:8+<1588::AID-CNCR9>3.0.CO;2-G. - DOI - PubMed

[2] Coleman RE. Skeletal complications of malignancy. Cancer. 1997;80:1588–94. doi: 10.1002/(SICI)1097-0142(19971015)80:8+<1588::AID-CNCR9>3.0.CO;2-G. - DOI - PubMed

[3] Rogers MJ, Gordon S, Benford HL, et al. Cellular and molecular mechanisms of action of bisphosphonates. Cancer. 2000;88:2961–78. doi: 10.1002/1097-0142(20000615)88:12+<2961::AID-CNCR12>3.0.CO;2-L. - DOI - PubMed

[4] Rogers MJ, Gordon S, Benford HL, et al. Cellular and molecular mechanisms of action of bisphosphonates. Cancer. 2000;88:2961–78. doi: 10.1002/1097-0142(20000615)88:12+<2961::AID-CNCR12>3.0.CO;2-L. - DOI - PubMed

[5] Kuo YC, Su CH, Liu CY, Chen TH, Chen CP, Wang HS. Transforming growth factor-beta induces CD44 cleavage that promotes migration of MDA-MB-435s cells through the up-regulation of membrane type 1-matrix metalloproteinase. Int J Cancer. 2009;124:2568–76. doi: 10.1002/ijc.24263. - DOI - PubMed

[6] Kuo YC, Su CH, Liu CY, Chen TH, Chen CP, Wang HS. Transforming growth factor-beta induces CD44 cleavage that promotes migration of MDA-MB-435s cells through the up-regulation of membrane type 1-matrix metalloproteinase. Int J Cancer. 2009;124:2568–76. doi: 10.1002/ijc.24263. - DOI - PubMed

[7] Martínez AS, Huelsken J. The niche under siege: novel targets for metastasis therapy. J Intern Med. 2013;274:127–36. doi: 10.1111/joim.12024. - DOI - PubMed

[8] Martínez AS, Huelsken J. The niche under siege: novel targets for metastasis therapy. J Intern Med. 2013;274:127–36. doi: 10.1111/joim.12024. - DOI - PubMed

[9] Coleman R, Gnant M, Morgan G, Clezardin P. Effects of bone-targeted agents on cancer progression and mortality. J Natl Cancer Inst. 2012;104:1059–67. doi: 10.1093/jnci/djs263. - DOI - PubMed

[10] Coleman R, Gnant M, Morgan G, Clezardin P. Effects of bone-targeted agents on cancer progression and mortality. J Natl Cancer Inst. 2012;104:1059–67. doi: 10.1093/jnci/djs263. - DOI - PubMed

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Bisphosphonates as anticancer agents in early breast cancer: preclinical and clinical evidence

Affiliations

Bisphosphonates as anticancer agents in early breast cancer: preclinical and clinical evidence

Authors

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