Tumour progression and angiogenesis in bone metastasis from breast cancer: new approaches to an old problem.

Breast cancer metastasizes frequently to the skeleton and causes considerable morbidity and deterioration of the quality of life. The clinical consequences of skeletal metastases are bone pain, pathological fractures, hypercalcaemia and nerve compression syndromes. From the moment breast cancer cells are located in the bone microenvironment, they may release factors which stimulate bone resorption and angiogenesis leading to growth of skeletal metastases and a subsequent selective increase in the attraction of new cancer cells to bone. In this review, emerging new concepts of breast cancer-bone interactions, in particular the involvement of angiogenesis, proteolysis and the role of cancer-induced bone resorption in skeletal metastasis are discussed. Better understanding of the processes involved in the metastasis of cancer cells to bone, local tumour growth and subsequent destruction of skeletal architecture can lead to optimal methods for the prevention and treatment of metastatic bone disease.