Bisphosphonates: Prevention of Bone Metastases in Breast Cancer
Bisphosphonates: Prevention of Bone Metastases in Breast Cancer
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DOI：
10.1007/978-3-642-21892-7_3
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发表时间：
2012-01-01
期刊：
影响因子：
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通讯作者：
Hadji, Peyman
中科院分区：
文献类型：
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作者：
Gnant, Michael;Dubsky, Peter;Hadji, Peyman
尽管在早期诊断、外科专业知识和辅助治疗方面取得了进展，但疾病复发和远处转移仍然是乳腺癌患者面临的挑战。骨是乳腺癌转移最常见的部位，骨微环境在窝藏播散性肿瘤细胞（DTC）中起着至关重要的作用，这是骨内外晚期复发的假定来源。因此，影响骨代谢的药物不仅可以预防骨病变的发生，而且可以显著降低骨内外复发的风险。双膦酸盐结合到矿化骨表面并被破骨细胞摄取，其中它们抑制骨质溶解，从而防止生长因子从骨基质释放。因此，骨微环境变得不利于DTC的存活和生长以及骨病变的形成。最近在乳腺癌辅助治疗中进行的唑来膦酸试验表明，患有早期乳腺癌的绝经前和绝经后女性的骨骼和其他部位的疾病复发率降低。基于辅助内分泌治疗期间已证实的骨保护作用，新的治疗指南建议常规使用双膦酸盐预防辅助治疗期间的骨丢失，这可能成为标准实践。
Disease recurrence and distant metastases remain challenging for patients with breast cancer despite advances in early diagnosis, surgical expertise, and adjuvant therapy. Bone is the most common site for breast cancer metastasis, and the bone microenvironment plays a crucial role in harboring disseminated tumor cells (DTCs), a putative source of late relapse in and outside bone. Therefore, agents that affect bone metabolism might not only prevent the development of bone lesions but also provide meaningful reductions in the risk of relapse both in bone and beyond. Bisphosphonates bind to mineralized bone surfaces and are ingested by osteoclasts, wherein they inhibit osteolysis, thereby preventing the release of growth factors from the bone matrix. Therefore, the bone microenvironment becomes less conducive to survival and growth of DTCs and bone lesion formation. Recent trials of zoledronic acid in the adjuvant setting in breast cancer have demonstrated reduced disease recurrence in bone and other sites in premenopausal and postmenopausal women with early breast cancer. Based on the proven effect of bone protection during adjuvant endocrine therapy, new treatment guidelines recommend the routine use of bisphosphonates to prevent bone loss during adjuvant therapy, which may likely become the standard practice.