Bone metabolic markers in the evaluation of bone scan flare phenomenon in bone metastases of breast cancer.

Bone scan flare seriously complicates evaluations of the therapeutic response of bone metastases. The value of bone metabolic markers in monitoring the therapeutic response for bone metastases in breast cancer was assessed. Twenty-three breast cancer patients with bone metastases treated by combined chemotherapy of cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) were monitored using bone scans; a bone resorption marker, pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP); a bone formation marker, bone-specific alkaline phosphatase (BAI-p); and a tumor-specific marker (CA15-3). Bone scans were performed before and 3 or 4 months after therapy. After CAF therapy, markers were measured monthly. As a control, the markers of nine patients without bone metastases who received adjuvant CAF therapy were also measured monthly. The therapeutic effect on bone metastases was assessed after the study. Five patients had progression of disease (PD), three had no change (NC), and 15 patients had partial responses (PR). Bone scan flare-up was seen in five PR patients. In patients who received adjuvant therapy, ICTP, BAI-p, and CA15-3 did not change. ICTP increased significantly in PD patients. ICTP did not increase in either NC or PR, including bone scan flare patients. BAI-p and CA15-3 did not show any discernible pattern among PD, PR, flare, and NC patients. Thus measuring ICTP could distinguish PD from NC or PR patients' responses to CAF therapy. This was true also for patients who showed bone scan flare-up. Measuring a bone resorption marker, ICTP, allows clinicians to monitor patients' responses to CAF therapy and may prevent prolonged ineffective therapy or unnecessary changes in therapy as a result of the flare phenomenon.