Factors influencing the role of bisphosphonates in breast cancer management.

Bone metastases represent a significant tumor-related complication affecting many breast cancer patients. The resulting bone destruction or osteolysis that frequently accompanies metastatic bone disease results in considerable morbidity for patients including a high rate of skeletal complications, severe pain, and a reduced quality of life. Traditionally, the treatment of metastatic bone disease has relied heavily on the use of multidisciplinary therapies, such as radiotherapy in combination with systemic treatment, supported by analgesia. Bisphosphonates are a class of pyrophosphate analogs that actively inhibit bone resorption. As a result, their clinical application has expanded greatly over the past 5 to 10 years and, in addition to being the treatment of choice for hypercalcemia of malignancy, they have been shown to be effective in reducing the skeletal morbidity associated with metastatic breast cancer. Furthermore, recent data from animal and in vitro studies suggest that bisphosphonates may actually have an antiapoptotic and antiproliferative effect not only on osteoclasts, but also on macrophages and tumor cells. Recent improvements in our understanding of the underlying molecular mechanisms in breast cancer, the diagnosis of the disease itself, and the development of new systemic therapies has led to improved survival benefit for many breast cancer patients. However, because survival duration has also been related to the risk of developing skeletal complications, bisphosphonates may play an ever greater role in the management and prevention of skeletal morbidity in the future.