Measurement of urinary collagen cross-links indicate response to therapy in patients with breast cancer and bone metastases

Objective assessment of response in bone metastases from breast cancer usin g radiological techniques takes up to 6 months of treatment to be certain o f a response, and sclerotic metastases are not evaluable. Standard serum an d 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 d evelopment of the urinary pyridinoline cross-link assays which measure matu re bone breakdown products have been shown to be highly sensitive and speci fic as a measure of bone change in osteoporosis. We have measured pyridinol ine (Pyr) and deoxypyridinoline (Dpyr) cross-links sequentially in 36 breas t cancer patients with bone metastases, to determine if the measurement of these analytes predicts response at an earlier stage than radiological asse ssment. Response was assessed by UICC criteria. Seventeen women responded t o hormonal therapy, whilst 19 developed progressive disease. Both Pyr and D pyr increased sequentially in women with progressive disease with changes b ecoming apparent by 8 weeks (P < 0.03), in responding women, cross-link lev els did not change significantly Pyr and Dpyr were more sensitive and speci fic than the standard serum tumour marker CA 15-3. Urinary cross-link measu rements 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.