Hypercalcaemia and breast cancer--an increased humoral component in patients with liver metastases

One hundred and forty-seven patients with hypercalcaemia and advanced breast cancer have been reviewed. One hundred and twenty-five (85%) had definite bone metastases but in 22 (15%) there was no radiographic evidence of skeletal involvement. Sixty-eight (46%) patients also had liver metastases. These were present in 15/22 (68%) without definite skeletal involvement and 53/125 (42%) with bone metastases (P = less than 0.05). In a series of 498 patients with first relapse in bone after primary treatment hypercalcaemia was more common after the development of liver metastases than in patients with disease remaining confined to the skeleton (31% v 15%; P = less than 0.001). A subsequent prospective biochemical study of 35 patients with hypercalcaemia suggested that a humoral factor was more pronounced in 18 with liver metastases. In this group renal tubular reabsorption of calcium was higher, serum phosphate and tubular reabsorption of phosphate lower, and cyclic AMP excretion was increased. The data suggest that there is an association between the presence of liver metastases and the development of hypercalcaemia in patients with breast cancer. The mechanisms by which liver involvement may contribute to the pathogenesis of hypercalcaemia are not known but could arise from either increased production or decreased clearance of a humoral factor.