Background. Sunitinib is a tyrosine kinase inhibitor used in the treatment of metastatic renal cell carcinoma. The main difficulty related to the treatment is the development of drug resistance followed by rapid progression of the disease. We analyzed tumor tissue of sunitinib treated patients in order to find miRNAs associated with therapeutic response. Methods. A total of 79 patients with metastatic renal cell carcinoma were included in our study. miRNA profiling in tumor tissue samples was performed by TaqMan Low Density Arrays and a group of selected miRNAs (miR-155, miR-374-5p, miR-324-3p, miR-484, miR-302c, and miR-888) was further validated by qRT-PCR. Normalized data were subjected to ROC and Kaplan-Meier analysis. Results. We reported decreased tissue levels of miR-155 and miR-484 as significantly associated with increased time to progression (miR-155: median TTP 5.8 versus 12.8 months, miR-484: median TTP 5.8 versus 8.9 months). Conclusion. miR-155 and miR-484 are potentially connected with sunitinib resistance and failure of the therapy. miR-155 is a known oncogene with direct influence on neovascularization. Biological role of miR-484 has to be clarified. Stratification of patients based on miRNA analysis would allow more personalized approach in therapy of metastatic renal cell carcinoma.

• MeSH
• dospělí MeSH
• indoly aplikace a dávkování   MeSH
• Kaplanův-Meierův odhad MeSH
• karcinom z renálních buněk farmakoterapie   genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• mikro RNA biosyntéza   genetika   MeSH
• nádorové biomarkery biosyntéza   genetika   MeSH
• patologická angiogeneze farmakoterapie   genetika   patologie   MeSH
• progrese nemoci MeSH
• pyrroly aplikace a dávkování   MeSH
• regulace genové exprese u nádorů MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Ovarian cancer (OC) represents a serious disease with high mortality and lack of efficient predictive and prognostic biomarkers. ATP-binding cassette (ABC) proteins constitute a large family dedicated to active transmembrane transport including transport of xenobiotics. MATERIALS AND METHODS: mRNA level was measured by quantitative RT-PCR in tumor tissues from OC patients. Bioinformatics analyses were applied to two gene expression datasets (60 primary tumors and 29 peritoneal metastases). Two different approaches of expression data normalization were applied in parallel, and their results were compared. Data from publically available cancer datasets were checked to further validate our conclusions. RESULTS: The results showed significant connections between ABC gene expression profiles and time to progression (TTP), chemotherapy resistance, and metastatic progression in OC. Two consensus ABC gene profiles with clinical meaning were documented. (a) Downregulation of ABCC4, ABCC10, ABCD3, ABCE1, ABCF1, ABCF2, and ABCF3 was connected with the best sensitivity to chemotherapy and TTP. (b) Oppositely, downregulation of ABCB11 and upregulation of ABCB1 and ABCG2 were connected with the worst sensitivity to chemotherapy and TTP. Results from publicly available online databases supported our conclusions. CONCLUSION: This study stressed the connection between two well-documented ABC genes and clinicopathological features-ABCB1 and ABCG2. Moreover, we showed a comparable connection also for several other ABC genes-ABCB11, ABCC4, ABCC10, ABCD3, ABCE1, ABCF1, ABCF2, and ABCF3. Our results add new clinically relevant information to this oncology field and can stimulate further exploration.

• MeSH
• ABC transportéry genetika   MeSH
• chemorezistence genetika   MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• nádory vaječníků genetika   patologie   MeSH
• peritoneální nádory genetika   sekundární   MeSH
• regulace genové exprese u nádorů * MeSH
• transkriptom MeSH
• výpočetní biologie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The aim of our study was to investigate whether microRNAs (miRNAs) could serve as predictive biomarkers to anti-EGFR therapy (cetuximab, panitumumab) in patients with RAS wild-type (wt-RAS) metastatic colorectal cancer (mCRC). Historical cohort of 93 patients with mCRC (2006-2009) was included and further divided into exploratory and validation cohorts. MiRNAs expression profiling was performed on the exploratory cohort of 41 wt-KRAS mCRC patients treated with cetuximab to identify miRNAs associated with time to progression (TTP). The validation was performed on two independent cohorts: 28 patients of wt-RAS mCRC treated with cetuximab and 24 patients of wt-RAS mCRC treated with panitumumab. We identified 9 miRNAs with significantly different expression between responders and non-responders to cetuximab therapy (P ≤ 0.01). These 9 miRNAs were further evaluated in two independent cohorts of patients and miR-31-3p (P < 0.001) and miR-31-5p (P < 0.001) were successfully confirmed as strongly associated with TTP in wt-RAS mCRC patients treated with cetuximab but not panitumumab. When evaluated on the complete cohort of cetuximab patients (N = 69), miR-31-3p (HR, 5.10; 95% CI, 2.52-10.32; P < 0.001) and miR-31-5p (HR, 4.80; 95% CI, 2.50-9.24; P < 0.001) were correlated with TTP on the comparable level of significance. There was no difference in miR-31-5p/3p expression levels in RAS mutated and wild-type tumor samples. MiR-31-5p/3p are promising predictive biomarkers of cetuximab response in wt-RAS mCRC patients.

• MeSH
• buňky HT-29 MeSH
• cetuximab terapeutické užití   MeSH
• dospělí MeSH
• erbB receptory antagonisté a inhibitory   MeSH
• HCT116 buňky MeSH
• kohortové studie MeSH
• kolorektální nádory farmakoterapie   genetika   metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA biosyntéza   genetika   MeSH
• monoklonální protilátky terapeutické užití   MeSH
• protinádorové látky aplikace a dávkování   terapeutické užití   MeSH
• ras proteiny genetika   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Na základe výsledkov nedávnych štúdií sa predpokladá, že za časť interindividuálnych rozdielov v liečebnej odpovedi môžu byť zodpovedné jednonukleotidové polymorfi - zmy v génoch niektorých membránových transportérov. Cieľom predkladanej práce bolo hodnotenie polymorfi - zmu 3435T > C (rs1045642) v géne pre mnohopočetnú liekovú rezistenciu 1 (MDR1, ABCB1), kódujúceho efl uxnú pumpu P-glykoproteín, vo vzťahu k liečebnej odpovedi u pacientok s karcinómom prsníka užívajúcich tamoxifén v adjuvantných režimoch. Efektivita antineoplastickej liečby vo vzťahu k jednotlivým genotypom polymorfi zmu sa posudzovala porovnaním času do progresie (TTP; n = 89). V našej štúdii sme u pacientok s genotypom TC polymorfi zmu MDR1 (3435T > C) zaznamenali signifi kantne najkratší TTP (TC vs. TT + CC: log-rank: 0,017, Breslow: 0,028, Tarone-Ware: 0,022; HR = 3,2, 95% CI: 1,23–8,33). Podobný trend bol zachovaný aj pri osobitnom hodnotení pacientok, u ktorých bol v čase diagnózy diagnostikovaný duktálny invazívny karcinóm (HR = 3,4; 95% CI: 0,94–12,10). Výsledky poukazujú na možný vplyv polymorfi zmu MDR1 (3435T > C) na vznik interindividuálnych rozdielov v liečebnej odpovedi na hormonálnu liečbu karcinómu prsníka.

Recent studies have demonstrated that single nucleotide polymorphisms (SNP) in genes of some membrane transporters can contribute to inter-individual differences in chemotherapy response. Our study was aimed to evaluate the relationship of 3435T > C (rs1045642) polymorphism in multidrug resistance-1 gene (MDR1, ABCB1), encoding an effl ux pump P-glycoprotein, to therapeutic outcome in breast cancer patients treated with tamoxifen received as an adjuvant treatment. Time to progression (TTP; n = 89) between genotypes of the tested SNP was investigated. Patients carrying TC genotype of MDR1 (3435T > C) were found to have signifi cantly the shortest TTP (TC vs. TT + CC: log-rank: 0,017, Breslow: 0,028, Tarone-Ware: 0,022; HR = 3,2, 95% CI: 1,23–8,33) in our study. A similar trend was also maintained for patients who were assessed at the time of diagnosis as ductal invasive carcinoma (HR = 3,4; 95% CI: 0,94–12,10). In conclusion, the results demonstrate that MDR1 (3435T > C) polymorphism could play the role in breast cancer inter-individual variability in therapeutic outcome to hormone therapy.

• MeSH
• časové faktory MeSH
• genotypizační techniky metody   přístrojové vybavení   MeSH
• geny MDR genetika   účinky léků   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• mnohočetná léková rezistence MeSH
• mutace MeSH
• nádory prsu * farmakoterapie   genetika   patologie   MeSH
• progrese nemoci MeSH
• tamoxifen terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Regulatory T (Treg) cells play an important role in the maintenance of immune system homeostasis. Multiple myeloma (MM) is a plasma cell disorder frequently associated with impaired immune cell numbers and functions. METHODS: We analyzed Treg cells in peripheral blood (n = 207) and bone marrow (n = 202) of pre-malignant and malignant MM patients using flow cytometry. Treg cells and their subsets from MM patients and healthy volunteers were functionally evaluated for their suppressive property. A cohort of 25 patients was analyzed for lymphocytes, CD4 T cells and Treg cells before and after treatment with cyclophosphamide, thalidomide plus dexamethasone (CTD). RESULTS: We found elevated frequencies of Treg cells in newly diagnosed (P<0.01) and relapsed MM patients (P<0.0001) compared to healthy volunteers. Also, Treg subsets including naïve (P = 0.015) and activated (P = 0.036) Treg cells were significantly increased in MM patients compared to healthy volunteers. Functional studies showed that Treg cells and their subsets from both MM and healthy volunteers were similar in their inhibitory function. Significantly increased frequencies of Treg cells were found in MM patients with adverse clinical features such as hypercalcemia (>10 mg/dL), decreased normal plasma cell (≤5%) count and IgA myeloma subtype. We also showed that MM patients with ≥5% of Treg cells had inferior time to progression (TTP) (13 months vs. median not reached; P = 0.013). Furthermore, we demonstrated the prognostic value of Treg cells in prediction of TTP by Cox regression analysis (P = 0.045). CTD treatment significantly reduced frequencies of CD4 T cells (P = 0.001) and Treg cells (P = 0.018) but not Treg cells/CD4 T cells ratio compared to pre-treatment. CONCLUSIONS: Our study showed immune deregulation in MM patients which is evidenced by elevated level of functionally active Treg cells and patients with increased Treg cells have higher risk of progression.

• MeSH
• CD4-pozitivní T-lymfocyty účinky léků   imunologie   MeSH
• cyklofosfamid terapeutické užití   MeSH
• dexamethason terapeutické užití   MeSH
• dospělí MeSH
• hyperkalcemie etiologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom komplikace   farmakoterapie   imunologie   patologie   MeSH
• prediktivní hodnota testů MeSH
• progrese nemoci MeSH
• proporcionální rizikové modely MeSH
• referenční hodnoty MeSH
• regulační T-lymfocyty účinky léků   imunologie   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• T-lymfocyty - podskupiny imunologie   MeSH
• thalidomid terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: Subtotal meningioma resection (STR) is often performed to minimize surgical morbidity. Nevertheless, only a few studies have reported on patient outcome after STR. We studied the long-term outcome of SIV (Simpson grade IV) resection and identified predictive factors of overall survival (OS), progression-free survival (PFS) and time to progression (TTP). METHODS: A retrospective analysis was performed on 68 patients who underwent SIV resection of meningioma (grade I) from 2004 to 2010. Data were collected from clinical, surgical and pathology records and radiological imaging. Long-term outcomes were evaluated at least 10 years after surgery. RESULTS: Permanent morbidity was 11.8%, 30-day mortality 2.9% and progression rate 50.0% for a median follow-up duration of 126.6 months. Median TTP was 86.2 months. Adjuvant SRS was the only significant factor associated with longer PFS (p = 0.0052) and TTP (p = 0.0079). Higher age (p = 0.0022), KPS (p = 0.0182), postoperative ECOG score (p = 0.0182) were reliable predictors of shortened OS and aSRS (p = 0.0445) was reliable predictor of longer OS. CONCLUSION: STR in intracranial meningioma is still viable and often the only treatment option available in high-risk patients or high-risk tumors. Although surgical morbidity and mortality are high, the OS rate was 85.3% at 5 years and 79.4% at 10 years. Because of the considerable progression rate and rather a long term OS the adjuvant SRS should be considered following SIV resection.

• MeSH
• adjuvantní radioterapie MeSH
• časové faktory MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• meningeální nádory mortalita   patologie   chirurgie   MeSH
• meningeom mortalita   patologie   chirurgie   MeSH
• míra přežití MeSH
• radiochirurgie MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň nádoru MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The RAISE phase III clinical trial demonstrated that ramucirumab + FOLFIRI improved overall survival (OS) [hazard ratio (HR) = 0.844, P = 0.0219] and progression-free survival (PFS) (HR = 0.793, P < 0.0005) compared with placebo + FOLFIRI for second-line metastatic colorectal carcinoma (mCRC) patients previously treated with first-line bevacizumab, oxaliplatin, and a fluoropyrimidine. Since some patient or disease characteristics could be associated with differential efficacy or safety, prespecified subgroup analyses were undertaken. This report focuses on three of the most relevant ones: KRAS status (wild-type versus mutant), age (<65 versus ≥65 years), and time to progression (TTP) on first-line therapy (<6 versus ≥6 months). PATIENTS AND METHODS: OS and PFS were evaluated by the Kaplan-Meier analysis, with HR determined by the Cox proportional hazards model. Treatment-by-subgroup interaction was tested to determine whether treatment effect was consistent between subgroup pairs. RESULTS: Patients with both wild-type and mutant KRAS benefited from ramucirumab + FOLFIRI treatment over placebo + FOLFIRI (interaction P = 0.526); although numerically, wild-type KRAS patients benefited more (wild-type KRAS: median OS = 14.4 versus 11.9 months, HR = 0.82, P = 0.049; mutant KRAS: median OS = 12.7 versus 11.3 months, HR = 0.89, P = 0.263). Patients with both longer and shorter first-line TTP benefited from ramucirumab (interaction P = 0.9434), although TTP <6 months was associated with poorer OS (TTP ≥6 months: median OS = 14.3 versus 12.5 months, HR = 0.86, P = 0.061; TTP <6 months: median OS = 10.4 versus 8.0 months, HR = 0.86, P = 0.276). The subgroups of patients ≥65 versus <65 years also derived a similar ramucirumab survival benefit (interaction P = 0.9521) (≥65 years: median OS = 13.8 versus 11.7 months, HR = 0.85, P = 0.156; <65 years: median OS = 13.1 versus 11.9 months, HR = 0.86, P = 0.098). The safety profile of ramucirumab + FOLFIRI was similar across subgroups. CONCLUSIONS: These analyses revealed similar efficacy and safety among patient subgroups with differing KRAS mutation status, longer or shorter first-line TTP, and age. Ramucirumab is a beneficial addition to second-line FOLFIRI treatment for a wide range of patients with mCRC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01183780.

• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• fluoruracil aplikace a dávkování   MeSH
• kamptothecin aplikace a dávkování   analogy a deriváty   MeSH
• Kaplanův-Meierův odhad MeSH
• kolorektální nádory farmakoterapie   genetika   patologie   MeSH
• leukovorin aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• monoklonální protilátky aplikace a dávkování   MeSH
• mutace MeSH
• přežití bez známek nemoci MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   MeSH
• protoonkogenní proteiny p21(ras) genetika   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Východiska: Karcinom slinivky břišní představuje čtvrtou nejčastější příčinu úmrtí na nádorová onemocnění celosvětově. Při porovnání s ostatními solidními nádory jsou léčebné výsledky ve všech stadiích onemocnění nejhorší. Soubor pacientů a metody: Do hodnocení bylo zařazeno 19 pacientů léčených ve 2. linii paliativní terapie kombinací gemcitabin + nab-paklitaxel pro lokálně pokročilý nebo metastazující karcinom slinivky břišní v období mezi říjnem 2014 a prosincem 2016 na Onkologické klinice 1. LF UK a VFN v Praze. Všichni nemocní absolvovali kombinovanou chemoterapii gemcitabin (1 000 mg/m2) + nab-paklitaxel (125 mg/m2) týdně s týdenní pauzou po třech aplikacích. Byl hodnocen protinádorový účinek (počet objektivních léčebných odpovědí (disease control rate – DCR), doba do progrese onemocnění (time to progression – TTP) a celkové přežití (overal survival – OS)) a výskyt nežádoucích účinků. Výsledky: Kontroly onemocnění bylo dosaženo dle RECIST kritérií u 9 pacientů (56,3 %, u 2 pacientů došlo k parciální regresi). Bylo dosaženo mediánu TTP 5,5 měsíce a medián OS dosáhl 10,1 měsíce. Závěr: U pacientů ve velmi dobrém výkonnostním stavu (0–1) s pokročilým karcinomem pankreatu může užití režimu gemcitabin + nab-paklitaxel ve 2. linii paliativní terapie vést k prodloužení TTP a OS při zachování dobré kvality života nemocných.

Introduction: Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. The outcomes at all stages of the disease are the worst among patients with solid tumors. Patients and Methods: Analyses were conducted on 19 patients treated with gamcitabine + nab-paclitaxel for locally advanced or metastatic pancreatic cancer as a second line treatment between October, 2014, and December, 2016, at Department of Oncology of First Faculty of Medicine and General University Hospital in Prague. Patients were treated with gemcitabine (1,000 mg/sqm) + nab-paclitaxel (125 mg/sqm) at days 1, 8 and 15 of each 28-day cycle. Antitumor efficacy (disease control rate (DCR), time to progression (TTP), and overall survival (OS)) and adverse events were monitored. Results: Disease control according to RECIST criteria was achieved in nine cases (56.3%, two partial regressions were observed). The median TTP was 5.5 months and median OS was 10.1 months. Conclusion: In patients with advanced or metastatic pancreatic cancer with good performance statuses (0–1) gemcitabine + nab-paclitaxel as a second line treatment led to a prolongation in time to progression and higher overall survival with good quality of life.

• MeSH
• analýza přežití MeSH
• deoxycytidin farmakologie   terapeutické užití   MeSH
• dospělí MeSH
• klinická studie jako téma MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory slinivky břišní * farmakoterapie   MeSH
• nežádoucí účinky léčiv MeSH
• paclitaxel farmakologie   terapeutické užití   MeSH
• přežití bez známek nemoci MeSH
• protinádorové látky farmakologie   terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

INTRODUCTION: The normalization of free light chain ratio (FLCr) has been introduced as a marker of stringent complete remission (CR) of multiple myeloma (MM). There is currently a lack of literature assessing the role of FLCr on MM disease progression and remission status. PATIENTS AND METHODS: A multicentered retrospective review of 125 patients with MM in CR and various FLCr values was completed. Parameters of interest included patient demographics, FLCr values, complete remission (CR)/relapse status, and time to progression (TTP). The FLCr values were recorded to provide time-dependent findings on the role of FLCr on progression-free survival and overall survival (OS). RESULTS: The mean follow-up time of 125 patients from five hospitals in the Czech Republic was 31 months. A total of 47.2% of patients relapsed (54 of 125) during the follow-up period. The median TTP of patients with normal FLCr (n = 66) was 54.4 and 40.2 months for patients with abnormal FLCr (n = 59) (P = 0.217). None of the patients reached median overall survival regardless of FLCr values (P = 0.821). In the subgroup of newly diagnosed patients after upfront autologous stem cell transplantation (ASCT), there were 55.6% of patients (35 of 63) with normal FLCr and 44.4% (28 of 64) with abnormal FLCr. A total of 34.9% of patients (22 of 63) relapsed in this subgroup. Within the abnormal FLCr patients, a median TTP was 56.3 months, but no median TTP was reached among the normal FLCr patients (P = 0.746). Median OS in patients with normal (nFLCr) and abnormal FLCr (aFLCr) was not reached (P = 0.787). CONCLUSION: We did not observe any benefit from FLCr normalization in CR in myeloma patients in terms of progression-free survival or overall survival.

• MeSH
• analýza přežití MeSH
• autologní transplantace MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• indukce remise MeSH
• lehké řetězce imunoglobulinů krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom krev   diagnóza   mortalita   terapie   MeSH
• následné studie MeSH
• prognóza MeSH
• progrese nemoci MeSH
• protinádorové látky MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

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.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• monoklonální protilátky terapeutické užití   MeSH
• nádorové biomarkery analýza   MeSH
• nádory prsu chemie   patologie   MeSH
• progrese nemoci MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• receptor erbB-2 analýza   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH