title: Zoledronic acid effectiveness against breast cancer metastases - a role for estrogen in the microenvironment?
abstract: Zoledronic acid (ZA) is an imidazole-containing bisphosphonate that has been extensively studied as an osteoclast inhibitor. ZA decreases bone turnover and has been effective in limiting osteolysis in metastatic cancers, including breast cancer. Recent clinical trials that demonstrated enhancement of disease-free survival by bisphosphonates have prompted interest in bisphosphonates as anti-cancer agents. ZA, for example, increased disease-free survival in postmenopausal and in premenopausal, hormone-suppressed breast cancer patients. Intriguingly, however, there was a lack of an anti-cancer effect of ZA in premenopausal women without ovarian suppression. These observations have prompted the conjecture that anti-cancer effects of ZA are limited to estrogen-poor environments. This review explores possible mechanisms compatible with differences in ZA activity in premenopausal women compared with postmenopausal (or hormone-suppressed) women.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Steinman
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brufsky
authors.forename: Steffi
authors.initials: S
authors.lastname: Oesterreich
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D007109:Immunity / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D015398:Signal Transduction; D059016:Tumor Microenvironment; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D004967:Estrogens; D007093:Imidazoles; D036341:Intercellular Signaling Peptides and Proteins; D000077211:Zoledronic Acid