Introduction: Women with non-metastatic breast cancer form a distinct subpopulation in which calcium homeostasis in response to treatment with denosumab has not been extensively investigated.
Methods: Female patients with osteoporosis, who were eligible for treatment with denosumab, were prospectively enrolled (20112012) and divided into two groups; Group A consisting of patients with either no history or benign diseases non affecting bone metabolism (n=24 controls) and Group B patients with non-metastatic breast cancer (n=18). Documentation of renal impairment, disorders of parathyroid function or the presence of bone metastases served as exclusion criteria. All patients were administered a single-dose of denosumab under standard calcium and vitamin D supplementation. Serum calcium, phosphorus, parathyroid hormone (iPTH) and 24 h urine calcium were measured at days 0, 7 and 180. Primary outcomes were the development of hypocalcaemia and secondary hyperparathyroidism.
Results: At baseline, groups were comparable in age, calcium and iPTH levels. No events of hypocalcaemia were recorded. Overall, incidence of secondary hyperparathyroidism was found to be 45.5% one week after administration of denosumab. Interestingly, at day 180 incidence of secondary hyperparathyroidism was higher in Group B in contrast to the pattern recorded in controls, although not reaching statistical significance. At day 7, iPTH was found to be significantly higher only in controls (Wilcoxon Signed Rank test: P=0.013) compared to group-specific baseline values. At day 180, borderline increase in iPTH of Group B was noted (P=0.08), whereas iPTH returned to baseline in controls.
Discussion: A pattern of delayed development of secondary hyperparathyroidism might be present in patients with non-metastatic breast cancer. It could be extrapolated that this finding might be associated with a partial functional defect in calcium sensing receptor, which has recently been implicated in the pathogenesis of breast cancer. The findings warrant further investigation.