The amino-terminal propeptide (PINP) of type I collagen is a clinically valid indicator of bone turnover and extent of metastatic spread in osseous metastatic breast cancer

Abstract

Background: The efficacy control for the treatment of bone metastases in breast cancer is difficult and usually initiated later and with longer time between treatment cycles than the restaging of visceral or soft tissue metastases. The amino-terminal propeptide (PINP) of type I collagen as a biochemical indicator of bone turnover might facilitate early and valid disease surveillance. The utility of total PINP was investigated in metastatic breast cancer patients, with or without bone metastases (for monitoring of therapy). The results were compared to the established markers, osteocalcin and beta-carboxyterminal telopeptide (CTX) or crosslaps concentration.

Patients and methods: Baseline serum samples of 51 patients with metastastic breast cancer under chemotherapy were investigated. In total, 38 patients had been diagnosed with bone metastases while 13 had no evidence of metastastic spread to the bone. All the patients with bone spread received bisphosphonates in addition to systemic chemotherapy and/or antibody therapy or hormonal treatment. Osteocalcin, CTX and PINP levels were measured on an Elecsys 2010 analyzer (electrochemiluminescence immunoassay--ECLIA). The normal cut-off values were: osteocalcin < 41.3 pg/ml, CTX < 1008 pg/ml and PINP < 95 ng/ml. Based on overall treatment outcome, the patients were grouped as responders (CR/PR), with stable disease (SD) or displaying primary progression (PD).

Results: The baseline levels of PINP were significantly higher in patients with bone metastases (median: 92.8 ng/ml) than in those without (median: 63.2 ng/ml, p = 0.044). Patients with more than seven bone metastases had significantly higher PINP levels (median: 149.7 ng/ml) than those with fewer than seven (median: 67.6 ng/ml, p = 0.04). Significant differences were also found for osteocalcin and CTX, at p = 0.02 and p = 0.04, respectively, although the median levels remained under the normal cut-off levels. In terms of response assessment of bone spread, the PINP concentrations decreased in responders from 194.3 ng/ml to 100.4 ng/ml (p = 0.23). In patients with SD, PINP remained at the same level of approximately 70 ng/ml (p = 0.16), but increased in patients with PD from 83.4 ng/ml to 176.5 ng/ml (p = 0.14). These trends rather than statistical difference were probably due to the limited patient cohort. No differences were found for the serum concentrations of PINP, CTX and osteocalcin between post- and pre-menopausal women.

Conclusion: The PINP levels of the osseous metastatic breast cancer patients were elevated at baseline in comparison to those without bone involvement; the levels correlated to the number of bone metastases but were independent of the menopausal status. Thus, the levels of PINP under therapy might correlate with the response to therapy. Osteocalcin and CTX did not show similar sensitivity for the surveillance of bone metastases.