Gálvez-Muñoz Elisa, Rodríguez-Lescure Álvaro
Servicio de Oncología Médica, Hospital General Universitario de Elche, Alicante, España.
Med Clin (Barc). 2010 Jun 12;135(2):70-4. doi: 10.1016/j.medcli.2009.10.013.
Breast cancer is the most common neoplasm in women. Bone is the most common site of metastatic spread from primary operable breast cancer, causing pain, fractures and hypercalcemia. This spread depends on the release of osteolytic substances by the cancer cells. The osteoclasts also release growth factors that can act back on the cancer cells to activate growth. Biphosphonates, antiosteolytic agents, have been shown to reduce the progression of established bone metastases. Emerging evidence suggests that biphosphonates also have antitumor and antimetastatic properties, including the inhibition of angiogenesis, tumor-cell invasion, and adhesion in bone; the induction of apoptosis; antitumor sinergy with cytotoxic chemotherapy; and immunomodulatory effects through induction of γ/δ T cells. These findings were the background and rationale for ongoing clinical trials, in order to establish their role as a part of adjuvant treatment for early breast cancer. The oral biphosphonate clodronate (1600mg/d) is effective in patients with bone metastases. When used as adjuvant therapy, given to patients with operable breast cancer for two years, clodronate has been reported to reduce the risk of bone metastases during a 2-year study period with a significant reduction in mortality. This benefit supports its use as additional adjuvant therapy for patients with operable breast cancer. Zoledronic acid, a potent nitrogen-containing biphosphonate, has been shown to maintain or increase bone mineral density (BMD) in premenopausal women with early-stage breast cancer receiving adjuvant hormone therapies as well as healthy postmenopausal women with low BMD. Recent large clinical trials with biphosphonates in the (neo)adjuvant setting for early-breast cancer, demonstrate an improvement of disease-free and overall survival as well as increased pathologic rate responses.
乳腺癌是女性中最常见的肿瘤。骨是原发性可手术乳腺癌转移扩散最常见的部位，会引起疼痛、骨折和高钙血症。这种扩散取决于癌细胞释放溶骨物质。破骨细胞也会释放生长因子，这些因子可作用于癌细胞以激活其生长。双膦酸盐类抗溶骨药物已被证明可减少已形成的骨转移的进展。新出现的证据表明，双膦酸盐还具有抗肿瘤和抗转移特性，包括抑制血管生成、肿瘤细胞在骨中的侵袭和黏附；诱导细胞凋亡；与细胞毒性化疗产生抗肿瘤协同作用；以及通过诱导γ/δT细胞产生免疫调节作用。这些发现是正在进行的临床试验的背景和理论依据，目的是确定它们作为早期乳腺癌辅助治疗一部分的作用。口服双膦酸盐氯屈膦酸（1600mg/d）对骨转移患者有效。当作为辅助治疗给予可手术乳腺癌患者两年时，据报道氯屈膦酸在一项为期2年的研究期间可降低骨转移风险，并显著降低死亡率。这一益处支持其作为可手术乳腺癌患者的额外辅助治疗。唑来膦酸是一种强效含氮双膦酸盐，已被证明可维持或增加接受辅助激素治疗的早期乳腺癌绝经前女性以及骨密度低的健康绝经后女性的骨矿物质密度（BMD）。最近在早期乳腺癌的（新）辅助治疗中使用双膦酸盐的大型临床试验表明，无病生存期和总生存期有所改善，病理缓解率也有所提高。
