The role of bisphosphonates in breast cancer: The present and future role of bisphosphonates in the management of patients with breast cancer

At least 25% of patients with breast cancer develop skeletal metastases, with bone the site of disease producing the greatest morbidity. Skeletal complications include hypercalcaemia, pathological fracture, bone pain requiring radiotherapy, and spinal cord or nerve root compression. Randomised trials in advanced breast cancer have shown that one of these major events occurs, on average, every 3–4 months [1,2]. The average life expectancy from diagnosis of bone metastases is 2 years, with up to 20% of patients surviving 5 years. There is thus a real need for treatment to reduce skeletal complications and to improve the quality of life in these individuals.Bone is not an inert organ; normal bone undergoes a continuous process of resorption and formation. Recent research has begun to shed new light on the development of bone metastases, as well as on the continual interaction between cancer cells and active bone. Tumour cells in the bone marrow cavity secrete a variety of paracrine factors that stimulate bone formation. Of key importance is the stimulation of osteoclast function. This results in osteolysis, which is typically associated with disruption of the normal coupling signals that control the relative levels of osteoblast and osteoclast function. It is in this situation that bisphosphonates are able to offer their therapeutic potential in metastatic disease. These abnormalities in bone function are reflected in abnormal levels of serum and urinary collagen breakdown products, which may therefore be exploited as biochemical markers to monitor progress of the disease and the effectiveness of bisphosphonate therapy.The breast cancer patient with skeletal metastases now has a much improved range of management options, including radiotherapy and radiopharmaceuticals, orthopaedic surgery and systemic anticancer therapy with cytotoxic and endocrine therapy [3]. Nevertheless, it is now apparent that the bisphosphonates present an important additional treatment strategy