Background: The presence of bone metastases (BMe) alters the balance of bone remodeling and consequently, levels of bone turnover markers (BTM). Increased levels of these biomarkers are related to the risk of skeletal-related events (SREs), disease progression and death. Treatment with bisphosphonates reduces the probability of SREs through osteoclastic activity inhibition. The aim of this study was to determine the relation between BTM, bone metastasis development and SREs, disease progression and death in patients with breast cancer (BC) and BMe.
Patients and methods: Observational, prospective and multicenter study. Patients with BC and BMe; no previous bone treatment in the last 6 months prior to study entry. Urinary aminoterminal telopeptide of collagen I (NTX, Osteomark NTx Urine, Wampole Laboratories, USA); urinary alpha-alpha-isomer of carboxyterminal telopeptide of collagen I (αα-CTX, ALPHA Crosslaps EIA, ids, UK) and serum bone alkaline phosphatase (BALP, OSTASE BAP, ids, UK) were determined at baseline (V0) and every 3 mo along 18 months (V6). Patients were treated with zoledronic acid (ZA) at inclusion and every 3–4 weeks.
Results: 234 patients with BC and BMe were analyzed. BTM results were available for 219 patients at basal visit (V0) and every 3 mo of treatment along 18 months (V6). Population basal characteristics (234 patients): mean age: 59.8 years; ER+: 80.3%; PR+: 64.9%; HER 2+: 18.3%. Patients with pathologic baseline levels were: 49.8% NTX, 39.6% αα-CTX and 83.4% BALP. A significant decrease was observed in BTM at V2 vs V0 after 6 months: 13.7%, 8.4% and 58.4% presented pathologic values of NTX, αα-CTX and BALP respectively. Normalized levels remained steady throughout 18 mo follow-up, finding significant decrease for each BMT for each time point except at V6 for αα-CTX. Regarding association between BTM and SREs, progression and exitus, a significant association was observed between pathologic levels of BTM throughout follow-up: with SRE at V3, V4 for NTX; with disease progression at V3, V4, V5, V6 for NTX, at V2 for αα–CTX and at each follow up visit for BALP; and with death at V1,4,5 for NTX, at V5 for αα–CTX and at V1,2,3,4,5 for BALP.
Conclusions: Addition of ZA to standard systemic therapy reduced BTM levels during the first 3 months of treatment and normalized levels remained steady throughout 18 months follow up except at Month 18 for αα-CTX. Pathological levels of BTM were significantly associated with SRE, disease progression and death.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-18.