Molecular pathogenesis of bone metastases in breast cancer: Proven and emerging therapeutic targets

Abstract

Metastatic occurrence is the principal cause of death in breast cancer patients. The high osteotropism makes breast cancer the most common primary tumor type associated with metastatic bone disease. The peculiar clinical aspects associated with metastases limited to the skeletal system suggest considering these cases as a distinctive subset of metastatic patients with a better prognosis. Because bone is frequently the first metastatic site in disease relapse, it is feasible that the next improvement in therapeutic options for bone metastatic disease could be associated with an improvement of survival expectation and quality of life in breast cancer patients. Study of the molecular basis of bone remodeling and breast cancer osteotropism has allowed identification of several therapeutic candidates involved in formation and progression of bone metastases. These targets are frequently the determinants of positive feedback between the tumor and bone cells whose clinical outcome is osteolytic lesions. In this review, we discuss the physiopathologic features underlying targeted therapeutic strategies aimed at interfering with the aberrant bone remodeling associated with breast cancer metastases.

Keywords: Breast cancer; Bone metastasis; Targeted therapy; Osteoclasts

Core tip: Breast cancer cells preferentially colonize bone sites during their metastatic diffusion. Bone microenvironment and tumor cells operate a reciprocal selective pressure that results in the formation of osteolytic lesion and tumor progression. Targeting the molecular factors involved in this interaction has been demonstrated to be an effective strategy in preventing the clinical morbidity associated with bone metastases. In this review, we summarize physiopathologic aspects of bone metastases from breast cancer and discuss the most promising therapeutic targets for their future clinical management.