Bisphosphonates as anticancer agents in early breast cancer: preclinical and clinical evidence.
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.
Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. d.santini@unicampus.it.
Daniele
D
Santini
Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. l.stumbo@unicampus.it.
Luciano
L
Stumbo
Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. c.spoto@unicampus.it.
Chiara
C
Spoto
Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. l.donofrio@unicampus.it.
Loretta
L
D'Onofrio
Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. f.pantano@unicampus.it.
Francesco
F
Pantano
Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. m.iuliani@unicampus.it.
Michele
M
Iuliani
Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. m.fioramonti@unicampus.it.
Marco
M
Fioramonti
Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. a.zoccoli@unicampus.it.
Alice
A
Zoccoli
Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. g.ribelli@unicampus.it.
Giulia
G
Ribelli
Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. v.virzi@unicampus.it.
Vladimir
V
Virzì
Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. b.vincenzi@unicampus.it.
Bruno
B
Vincenzi
Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy. g.tonini@unicampus.it.
Giuseppe
G
Tonini
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D006801:Humans
D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates