Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
Adv Exp Med Biol. 2019;1152:105-129. doi: 10.1007/978-3-030-20301-6_7.
Bone is the most common site of metastasis for breast cancer. Bone metastasis significantly affects both quality of life and survival of the breast cancer patient. Clinically, complications secondary to bone metastasis include pain, pathologic fractures, spinal cord compression, and hypercalcemia of malignancy. Because bone metastasis is extremely common in patients with metastatic breast cancer, clinical management of bone metastases is an important and challenging aspect of treatment in the metastatic setting.The skeleton is a metabolically active organ system that undergoes continuous remodeling throughout life. A delicate balance of the bone-forming osteoblasts and bone-resorbing osteoclasts in the dynamic microenvironment of the skeleton maintains normal bone remodeling and integrity. The presence of metastatic lesions in bone disrupts the normal bone microenvironment and upsets the fine balance between the key components. The changes in the bone microenvironment then create a vicious cycle that further promotes bone destruction and tumor progression.Various therapeutic options are available for bone metastases of breast cancer. Treatment can be tailored for each patient and, often requires multiple therapeutic interventions. Commonly used modalities include local therapies such as surgery, radiation therapy and radiofrequency ablation (RFA) together with systemic therapies such as endocrine therapy, chemotherapy, monoclonal antibody-based therapy, bone-enhancing therapy and radioisotope therapy. Despite the use of various therapeutic modalities, bone metastases eventually become resistant to therapy, and disease progresses.In this chapter, we describe the clinical picture and biological mechanism of bone metastases in breast cancer. We also discuss known risk factors as well as detection and assessment of bone metastases. We present therapeutic options for bone metastasis using a multidisciplinary approach. Further, we describe future directions for bone metastasis management, focusing on novel bone-specific targeted therapies.
骨骼是乳腺癌最常见的转移部位。骨转移显著影响乳腺癌患者的生活质量和生存。临床上,骨转移的并发症包括疼痛、病理性骨折、脊髓压迫和恶性高钙血症。由于转移性乳腺癌患者的骨转移极为常见,因此骨转移的临床管理是转移性疾病治疗中的一个重要且具有挑战性的方面。骨骼是一个代谢活跃的器官系统,在整个生命过程中不断进行重塑。骨骼动态微环境中的成骨细胞和破骨细胞的精细平衡维持着正常的骨重塑和完整性。骨转移病灶的存在破坏了正常的骨微环境,打破了关键成分之间的微妙平衡。骨微环境的变化继而形成一个恶性循环,进一步促进骨破坏和肿瘤进展。针对乳腺癌的骨转移有多种治疗选择。可以根据每位患者的情况量身定制治疗方案,通常需要多种治疗干预。常用的方法包括局部治疗,如手术、放疗和射频消融术(RFA),以及全身治疗,如内分泌治疗、化疗、单克隆抗体治疗、骨增强治疗和放射性同位素治疗。尽管使用了各种治疗方法,但骨转移最终会对治疗产生耐药性,疾病会进展。在本章中,我们描述了乳腺癌骨转移的临床表现和生物学机制。我们还讨论了已知的危险因素,以及骨转移的检测和评估。我们采用多学科方法介绍了骨转移的治疗选择。此外,我们还描述了骨转移管理的未来方向,重点是新型骨特异性靶向治疗。