title: Serum 1,25-dihydroxyvitamin D may be related inversely to disease activity in breast cancer patients with bone metastases.
abstract: 1,25-dihydroxyvitamin D (1,25-(OH)2D) stimulates differentiation and controls proliferation in breast cancer cells. The role of endogenous 1,25-(OH)2D and its relation to PTH related protein (PTHrP) during the progression of breast cancer is not known; we therefore investigated these hormones in two studies. In a cross-sectional study of patients with breast cancer at different stages of disease, serum 1,25-(OH)2D levels (mean +/- SE) were highest in early disease (102 +/- 3.7 pmol/L), fell in normocalemic patients with bone metastases (52 +/- 5.3 pmol/L; P < 0.01), and were lowest in hypercalcemic patients (33 +/- 5.6 pmol/L; P < 0.001). PTHrP was detectable in the serum of only one normocalcemic patient with progressive metastases but was present in 11 of the 12 hypercalcemic patients, thus PTHrP did not stimulate 1,25-(OH)2D synthesis. In a 6-month longitudinal study of normocalcemic patients with bone metastases undergoing hormonal therapy, serum 1,25-(OH)2D concentrations fell in patients whose disease progressed (P = 0.0056), but remained constant in those who were stable or responded to treatment. These changes in 1,25-(OH)2D preceded clinical signs of progression and predicted disease response. In the progressive group, five of whom died during the study, 1,25-(OH)2D decreased between the initial and final samples, PTH fell significantly from 24.8 to 13.5 ng/L (P = 0.025), serum calcium rose from 2.27 to 2.39 mmol/L (P = 0.017), and the urinary calcium/creatinine ratio rose from 0.37 to 0.68 (P = 0.046). PTH and 1,25-(OH)2D were significantly correlated in the final samples from this group, Spearman's rank correlation = 0.80, P = 0.022. The results indicate that normocalcemia in these patients is maintained, at the expense of suppressing PTH and 1,25-(OH)2D, in the face of increased calcium released from lytic lesions in bone. Loss of the antiproliferative effects of 1,25-(OH)2D may then permit more rapid secondary growth of the tumor.
authors.affiliation: University of Manchester Bone Disease Research Centre, Department of Medicine, Manchester Royal Infirmary, United Kingdom.
authors.forename: E B
authors.initials: EB
authors.lastname: Mawer
authors.forename: J
authors.initials: J
authors.lastname: Walls
authors.forename: A
authors.initials: A
authors.lastname: Howell
authors.forename: M
authors.initials: M
authors.lastname: Davies
authors.forename: W A
authors.initials: WA
authors.lastname: Ratcliffe
authors.forename: N J
authors.initials: NJ
authors.lastname: Bundred
mesh_terms: D001859:Bone Neoplasms / Q000097:blood* / Q000556:secondary*; D001943:Breast Neoplasms / Q000097:blood*; D002117:Calcitriol / Q000097:blood*; D002118:Calcium / Q000652:urine; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood; D008137:Longitudinal Studies; D010281:Parathyroid Hormone / Q000097:blood; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000378:metabolism
chemical_list: C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D002117:Calcitriol; D002118:Calcium