Osteolytic bone metastases in breast carcinoma pathogenesis, morbidity and bisphosphonate treatment

In this review different aspects of osteolytic bone metastasis of breast carcinoma including morbidity, pathogenesis, accompanying hypercalcaemia and treatment, are discussed. Bone metastases occur in many patients with breast cancer (percentages of up to 85% have been reported); although patients seldom die of bone metastases morbidity is pronounced. Literature data point out that humoral factors, such as prostaglandins and the recently described growth factors are of importance beside cell interactions between monocytes, lymphocytes, osteoclasts and tumour cells. Nowadays, no significance is attributed to parathyroid hormone (PTH) overproduction in this respect. The differential diagnosis between primary hyperparathyroidism and tumour-induced hypercalcaemia is not always easy biochemically; combinations of both do occur less frequently than has been assumed in the past. A new and promising line of investigations involves the growth factors, which can increase osteolytic bone resorption and may bind to epidermal growth factor (EGF) or PTH receptors, thus inducing some of the biological effects of PTH (including hypercalcaemia). Until recently it was exceedingly difficult to treat tumour-induced hypercalcaemia (TIH) (the acute condition). Since the availability of the bisphosphonates dichloromethylidene bisphosphonate (Cl2MDP) and 3-amino-1-hydroxypropylidene-1, l-bisphosphonate (APD) this treatment has become very simple. Preliminary results, derived from the literature, point out that bisphosphonate treatment might also be effective in providing long-term control.