Increased prevalence of primary hyperparathyroidism in treated breast cancer

Hypercalcemia occurring in patients with advanced breast cancer (BC) is gen erally due to osteolytic metastases or to the activity of circulating tumor -derived products. In these conditions, the production of endogenous PTH is reduced. The frequency of hypercalcemia due to primary hyperparathyroidism in breast cancer is unknown. We examined the occurrence of primary hyperpa rathyroidism in a large group of women with treated BC. A total of 100 cons ecutive women aged 28-80 years with treated breast cancer were enrolled. On e hundred and two healthy age-matched women and 60 age-matched female patie nts with differentiated thyroid carcinoma examined before thyroidectomy wer e used as controls. Intact serum PTH and serum calcium were measured in all patients and controls. Hypercalcemia associated with elevated serum PTH co ncentration indicating primary hyperparathyroidism was found in 7 BC patien ts (7%) and in none of healthy women or patients with thyroid cancer. The p re-operative staging of BC patients with primary hyperparathyroidism was I in six and II in one of them, and no patient had evidence of distant metast ases. A parathyroid adenoma was found in all 6 BC patients submitted to nec k exploration, one patient refused surgery. Serum calcium and PTH concentra tions returned to normal levels after surgery. Two BC patients had increase d serum PTH and normal calcium concentrations. One of them had low serum 25 -hydroxyvitamin D [25(OH)D]. One patient with spread bone metastases had ne oplastic hypercalcemia with undetectable serum PTH concentration. All remai ning 90 BC patients had serum calcium and PTH concentrations within normal limits, but their mean (+/- SD) values (9.6 +/-0.5 mg/dl for serum calcium, 38.0 +/- 16.4 mg/dl for serum PTH) were slightly but significantly greater than in normal controls (9.3 +/-0.5 mg/dl, p=0.003 and 27.9 +/- 10.6 pg/ml , p=0.0001, respectively) and in patients with thyroid cancer (9.2 +/-0.6 m g/dl, p=0.001 and 26.2 +/- 11.0 pg/ml, p=0.001), with no relationship with clinical staging or anti-tumor therapy. In conclusion: 1) an increased freq uency of parathyroid adenoma was found in BC patients with mildly aggressiv e neoplastic disease; 2) in BC patients with no evidence of primary hyperpa rathyroidism mean serum PTH and calcium concentrations were significantly g reater than in healthy controls and in patients with thyroid carcinoma; and 3) this finding was unrelated to clinical staging or anti-tumor therapy. T hus, primary hyperparathyroidism should be considered as a possible cause o f hypercalcemia in patients with non-aggressive breast cancer. We suggest t hat serum PTH should be determined in all BC patients with increased serum calcium concentration, especially in those with no evidence of metastatic d isease.