Cíl studie: U 60 nemocných s karcinomem prsu jsme vyšetřovali sérové hladiny markeru novotvorby kostí, prokolagen typu 1 N-terminální propeptidu (P1NP) a markerů kostní resorpce, β-CrossLaps (β-CTX) a C-Telopeptid kolagenu typu I (ICTP). U 44 nemocných byly přítomny kostní metastázy a byly léčeny bisfosfonáty, 16 nemocných bylo bez přítomnosti metastatického procesu. Cílem studie bylo vyhodnotit senzitivitu a specifi citu vzhledem k přítomnosti kostních metastáz a efektu terapie bisfosfonáty. Metody: Sérové hladiny kostních markerů β-CrossLaps (CTX) a P1NP jsme stanovovali na analyzátoru Elecsys 2010 (Roche), ICTP byl stanovován manuální EIA metodou (Orion – Diagnostica). Nemocným s prokázanými kostními metastázami (n = 44) byla aplikována terapie bisfosfonáty (Zoledronat 4 mg/28 dní). Analýza kostních markerů byla prováděna před zahájením terapie a 14., 28. a 56. den terapie. Výsledky: Nejvyšší validitu vyšetření pro detekci kostních metastáz karcinomu prsu a reakci na terapii jsme prokázali pro ICTP (specifi cita 89,5% a senzitivita 79,5%). Závěr: Z dosažených výsledků se ICTP jeví jako specifi cký marker kostní remodelace a představuje citlivou a snadnou metodu detekce kostních metastáz i monitorování efektu jejich terapie., Objective: Biochemical markers of bone formation such as procollagen of type 1 N-terminal propeptide (P1NP) and bone resorption such as beta-CrossLaps (β-CTX) and cross linked c-telopeptide of type I collagen (ICTP) are considered possible non-invasive markers of bone metastases. Our objective was to determine validity of bone markers in the detection of bone metastases and in response to bisphosphonate therapy. Methods: We investigated 60 patients with breast carcinoma: 16 without bone metastases and 44 with metastases treated with Zoledronat 4 mg/28 days. Serum concentrations of β-CTX and P1NP were measured using immunoanalyser Elecsys 2010 (Roche) and ICTP by manual competitive immunoassay (Orion Diagnostica). Determinations of bone markers were performed prior to bisphosphonate therapy and after 2 weeks, 1 month and 2 months during therapy. Results: ICTP proved to have the highest diagnostic validity in detection of bone metastases reaching (specifi city 89,5% and sensitivity 79,5%). Conclusion: ICTP is a highly specifi c marker of bone degradation useful in diagnosis of bone metastases and monitoring of therapeutical effect of bisphosphonate., Nekulová Miroslava, Dubská L., Petráková K., Šimíčková M., Brančíková D., Pecen L., Pilný R., Valík D., and Lit.: 24
Trastuzumab is a humanized monoclonal antibody directed against the HER-2 receptor. Trastuzumab-based therapy significantly improves response rate (RR), time to progression (TTP) and overall survival (OS) for women with HER-2 positive metastatic breast cancer. Despite its initial efficacy, acquired resistance to trastuzumab develops in a majority of patients with MBC, and a large subset never responds, demonstrating primary resistance. The purpose of this retrospective study was to determine prognostic factors applicable to clinical practice. METHODS: We enrolled 112 women with metastatic breast cancer, who started the trastuzumab-based therapy at Masaryk Memorial Cancer Institute until January 2007. Clinical and laboratory factors, such as: patients conditions, character ofmetastatic spread, histology, estrogen, progesterone and Her-2 receptor status, Her-2/neu gene amplification, and serum tumor markers CEA, CA 15-3 and extracellular domain of Her-2 receptor (S-HER-2 ECD) were monitored. The association of all factors to response to therapy, time to progression (TTP) and overall survival (OS) was assessed. RESULTS: In 95% patients, the trastuzumab was combined with cytostatics (83% taxanes), 88,4% of patients started the trastuzumab as the first or second-line anticancer treatment. The median TTP was 284 days (9,3 months) and the median OS was 612 days (20,1 months) for all patients, RR was 54,5%. The highest RR was associated with the first-line treatment (p<0.0001) and with HER-2 gene/Chromosome 17 ratio > 2,2 (p=0,0092). Eleven patients (9,8%) discontinued the treatment because of toxicity, 7 patients did it as a result of cardiotoxicity (6,2%). CNS metastases occurred in 31 patients (27,7%). The S-HER-2 ECD was the most frequently elevated serum marker at the time of the treatment initialization (72,5%) and at the time of the progression (55,9%). Cox regression analysis identified S-HER-2 ECD levels at the beginning and between day 90 and 130 of the trastuzumab therapy as the best predictors of TTP. On the other hand the best predictor of OS was level of CEA before the treatment started and level of S-HER-2 ECD between day 90 and 130 of the trastuzumab therapy. CONCLUSIONS: We confirmed that the only one predictive marker for response to trastuzumab therapy is a proof of HER-2 tumor positivity.The highest prevalence of S-HER-2 ECD positivity among serum tumor markers and the strong association between initial and subsequent S-HER-2 ECD serum concentrations and time to progression and overall survival make the S-HER-2 ECD the most significant prognostic marker., Svoboda Marek, Grell Peter, Šimíčková Marta, Fabian Pavel, Petráková Katarína, Palácpvá Markéta, Macková Dagmar, Trojanec Radek, Hajdúch Marián, Pavlík Tomáš, Nenutil Rudolf, Vyzula Rostislav, and Lit.: 37