Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
Anticancer Agents Med Chem. 2012 Feb;12(2):114-22. doi: 10.2174/187152012799014931.
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.
尽管在外科手术和辅助治疗方面取得了进展，但仍有一部分早期乳腺癌患者会出现疾病复发和/或远处转移。人们认为骨髓中的播散性肿瘤细胞（DTCs）是导致骨及其他组织晚期复发的根源。骨骼是乳腺癌转移最常见的部位，因此，改变骨骼微环境的药物可能会影响疾病进程。双膦酸盐是一种有效的骨骼靶向治疗选择，可用于预防有乳腺癌的绝经前和绝经后妇女因癌症治疗引起的骨质流失（CTIBL）。双膦酸盐可抑制破骨细胞介导的骨质吸收，从而抑制释放促进癌细胞在骨骼中生长、分化和肿瘤形成所必需的生长因子。临床前和临床数据还表明细胞毒性化疗药物与双膦酸盐之间具有协同抗癌作用。最近的临床试验表明，唑来膦酸在乳腺癌辅助治疗中的应用可降低骨骼和其他部位的疾病复发率。目前，正在进行几项临床试验，以评估抗吸收剂是否可以抑制乳腺癌的疾病复发和骨转移的发展。基于最近的数据，双膦酸盐在乳腺癌治疗中的作用预计将在未来扩大。随着治疗指南的最新变化，在辅助治疗期间使用双膦酸盐预防骨质流失可能成为标准治疗方法，尤其是对接受内分泌治疗的患者。此外，根据正在进行的临床研究，唑来膦酸降低复发风险的作用正在显现。
