title: Measurement of urinary collagen cross-links indicate response to therapy in patients with breast cancer and bone metastases.
abstract: Objective assessment of response in bone metastases from breast cancer using radiological techniques takes up to 6 months of treatment to be certain of a response, and sclerotic metastases are not evaluable. Standard serum and urinary tumour markers may not always be utilized to predict response, as they may not be elevated, and therefore may not change on treatment. The development of the urinary pyridinoline cross-link assays which measure mature bone breakdown products have been shown to be highly sensitive and specific as a measure of bone change in osteoporosis. We have measured pyridinoline (Pyr) and deoxypyridinoline (Dpyr) cross-links sequentially in 36 breast cancer patients with bone metastases, to determine if the measurement of these analytes predicts response at an earlier stage than radiological assessment. Response was assessed by UICC criteria. Seventeen women responded to hormonal therapy, whilst 19 developed progressive disease. Both Pyr and Dpyr increased sequentially in women with progressive disease with changes becoming apparent by 8 weeks (P<0.03). In responding women, cross-link levels did not change significantly. Pyr and Dpyr were more sensitive and specific than the standard serum tumour marker CA 15-3. Urinary cross-link measurements provide a novel objective method of assessing response to treatment in women with bone metastases. Initial elevated urinary cross-link markers identify patients who tend not to respond to changes in hormonal therapy.
authors.affiliation: Department of Surgery, University Hospital of South Manchester, UK.
authors.forename: J
authors.initials: J
authors.lastname: Walls
authors.forename: A
authors.initials: A
authors.lastname: Assiri
authors.forename: A
authors.initials: A
authors.lastname: Howell
authors.forename: E
authors.initials: E
authors.lastname: Rogers
authors.forename: W A
authors.initials: WA
authors.lastname: Ratcliffe
authors.forename: R
authors.initials: R
authors.lastname: Eastell
authors.forename: N J
authors.initials: NJ
authors.lastname: Bundred
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000652:urine*; D014408:Biomarkers, Tumor / Q000652:urine*; D001859:Bone Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D003432:Cross-Linking Reagents; D018450:Disease Progression; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000596:Amino Acids; D014408:Biomarkers, Tumor; D003432:Cross-Linking Reagents; D004965:Estrogen Antagonists; C015484:pyridinoline; C036020:deoxypyridinoline