title: Anticancer activity of bisphosphonates in breast cancer.
abstract: Despite progress in surgical and adjuvant therapy, a subset of patients with early stage breast cancer experience disease recurrence and/or distant metastases. Disseminated tumor cells (DTCs) in the bone marrow are believed to be the source of late relapses in bone and other tissues. Bone is the most common site of breast cancer metastasis, and agents that modify the bone microenvironment could therefore affect the disease course. Bisphosphonates are an effective bone-targeted therapeutic option for preventing cancer treatment- induced bone loss (CTIBL) in pre- and postmenopausal women with breast cancer. Bisphosphonates inhibit osteoclast-mediated bone resorption, thereby inhibiting the release of growth factors necessary to promote cancer cell growth, differentiation, and tumor formation in bone. Preclinical and clinical data also suggest anticancer synergy between cytotoxic chemotherapy agents and bisphosphonates. Recent trials of zoledronic acid in the adjuvant setting in breast cancer have demonstrated reduced disease recurrence in bone and other sites. Currently, several ongoing clinical trials are evaluating whether antiresorptives can inhibit disease recurrence and the development of bone metastases from breast cancer. Based on recent data, the role of bisphosphonates in the breast cancer setting is expected to expand in the future. With recent changes to treatment guidelines, routine use of bisphosphonates to prevent bone loss during adjuvant therapy is likely to become standard practice, especially for patients receiving endocrine therapy. Furthermore, the use of zoledronic acid to reduce the risk of recurrence is emerging based on ongoing clinical research.
authors.affiliation: Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria. michael.gnant@meduniwien.ac.at
authors.forename: Michael
authors.initials: M
authors.lastname: Gnant
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000517:prevention & control / Q000556:secondary; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid