Expression profiling of human primary breast cancer tissue before treatment with gemcitabine, epirubicine and docetaxel
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Thuerigen O
PROVIDER: S-ECPF-GEOD-4056 | biostudies-other | 2006 Apr
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Gene expression profiles of human breast cancer tissues from 100 different patients treated with primary systemic chemotherapy (Gemcitabine, Epirubicin and Docetaxel) Keywords: expression profiling
2006-01-21 | GSE4056 | GEO
Project description:Gene expression profiles of human breast cancer tissues from 100 different patients treated with primary systemic chemotherapy (Gemcitabine, Epirubicin and Docetaxel) Keywords: expression profiling Human breast cancer tissues from 100 patients have been used to perform expression profiling analysis.
2006-01-21 | E-GEOD-4056 | biostudies-arrayexpress
Project description: Not available
| S-ECPF-MTAB-1614 | biostudies-other
Project description:In two randomized phase III trials of patients with metastatic breast cancer (MBC), gemcitabine-docetaxel (GD) and capecitabine-docetaxel (CD) had similar efficacy, but distinct safety profiles. Methods. Data from two GD versus CD studies were pooled; overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) were determined. Cox proportional hazards models identified prognostic factors associated with improved OS and PFS. Using a multivariate prognostic model incorporating identified adverse prognostic factors, we grouped MBC patients into low-, intermediate-, and high-risk categories. Hazard ratios (HRs) of GD over CD for OS and PFS were determined for subsets of patients. Results. Baseline demographics of the pooled population were mostly well balanced. In the pooled population, there were no significant differences between GD versus CD for OS (HR = 1.02; p = .824), PFS (HR = 1.15; p = .079), and ORR (p = .526). In the pooled crossover population, there were trends toward improved OS (HR = 0.82; p = .171) and PFS (HR = 0.93; p = .557) with GD. Several prognostic factors (including prior adjuvant taxane) for improved OS or PFS were identified; however, there were no significant interactions between treatment arms and prognostic factors for PFS or OS, except number of metastatic sites. In the prognostic model, median OS and PFS were numerically lower in the high-risk group versus the intermediate- and low-risk groups. Conclusion. This analysis confirms the lack of efficacy difference between GD and CD in the pooled population, crossover population, and almost all subpopulations. Several prognostic factors were associated with improved outcomes in the pooled population.
| S-EPMC4012969 | biostudies-literature
Project description:BACKGROUND:Alternating administration of docetaxel and gemcitabine might result in improved time-to-treatment failure (TTF) and fewer adverse events compared with single-agent docetaxel as treatment of advanced breast cancer. PATIENTS AND METHODS:Women diagnosed with advanced breast cancer were randomly allocated to receive 3-weekly docetaxel (group D) or 3-weekly docetaxel alternating with 3-weekly gemcitabine (group D/G) until treatment failure as first-line chemotherapy. The primary end point was TTF. RESULTS:Two hundred and thirty-seven subjects were assigned to treatment (group D, 115; group D/G, 122). The median TTF was 5.6 and 6.2 months in groups D and D/G, respectively (hazard ratio 0.85, 95% confidence interval 0.63-1.16; P = 0.31). There was no significant difference in time-to-disease progression, survival, and response rate between the groups. When adverse events were evaluated for the worst toxicity encountered during treatment, there was little difference between the groups, but when they were assessed per cycle, alternating treatment was associated with fewer severe (grade 3 or 4) adverse effects (P = 0.013), and the difference was highly significant for cycles when gemcitabine was administered in group D/G (P < 0.001). CONCLUSION:The alternating regimen was associated with a similar TTF as single-agent docetaxel but with fewer adverse effects during gemcitabine cycles.
| S-EPMC2860103 | biostudies-literature
Project description:BackgroundThe purpose of the present study was to retrospectively evaluate whether copy number changes of the genes encoding the ribonucleotide reductase subunit M1 (RRM1) and/or subunit M2B (RRM2B) predict sensitivity to gemcitabine administered in combination with docetaxel compared to single agent docetaxel in advanced breast cancer patients.MethodsPrimary tumor samples from patients randomly assigned to gemcitabine plus docetaxel or docetaxel alone were analyzed for RRM1 and RRM2B copy number changes using Fluorescence In Situ Hybridization (FISH) technology with probes covering respectively RRM1 at 11p15.5 and a reference probe covering the centromere of chromosome 11 (CEN-11), and RRM2B at 8q22.3 and a reference probe covering the centromere of chromosome 8 (CEN-8). The assays were validated in a material of 60 normal breast samples. Time to progression (TTP) was the primary endpoint. Overall survival (OS) and response rate (RR) were secondary endpoints. Associations between RRM1/CEN-11 and/or RRM2B/CEN-8 ratios and time-to-event endpoints were analyzed by unadjusted and adjusted Cox proportional hazards regression models. Heterogeneity of treatment effects on TTP and OS according to gene status were investigated by subgroup analyses, and the Wald test was applied. All statistical tests were two-sided.ResultsFISH analysis for both RRM1 and RRM2B was successful in 251 patients. RRM1 and RRM2B aberrations (deletions and amplifications) were observed in 15.9% and 13.6% of patients, respectively. RRM1 aberrations were associated with a decreased OS in the time interval 1.5-7.4 years (hazard ratio = 1.72, 95% confidence interval = 1.05-2.79, P = 0.03). RRM2B aberrations alone or in combination with RRM1 aberrations had no prognostic impact in terms of TTP or OS. RR was not different by gene status. No significant differences were detected in TTP or OS within subgroups according to gene status and chemotherapy regimen.ConclusionsThis study demonstrated the presence of RRM1 and RRM2B copy number changes in primary breast tumor specimens. Nevertheless, we found no support of the hypothesis that aberrations of RRM1 or RRM2B, neither individually nor in combination, are associated with an altered clinical outcome following chemotherapy with gemcitabine in combination with docetaxel compared to docetaxel alone in advanced breast cancer patients.
| S-EPMC3840598 | biostudies-literature
Project description:These patients were sensitive to docetaxel treatment, exhibiting less than 25% residual tumor.
| S-ECPF-GEOD-350 | biostudies-other
Project description:Lymph node involvement is the most important prognostic factor in breast cancer, but little is known about the underlying molecular changes. First, to identify a molecular signature associated with nodal metastasis, gene expression analysis was performed on a homogeneous group of 96 primary breast tumors, balanced for lymph node involvement. Each tumor was diagnosed as a poorly differentiated, estrogen positive, her2-neu negative invasive ductal cancer. (Affymetrix Human U133 Plus 2.0 microarray chips). A model, including 241 genes was built and validated on an internal and external dataset performed with Affymetrix technology. All samples used for validation had the same characteristics as the initial tumors. The area under the ROC curve (AUC) for the internal dataset was 0.646 and 0.651 for the external datasets. Thus, the molecular profile of a breast tumor reveals information about lymph node involvement, even in a homogeneous group of tumors. However, an AUC of 0.65 indicates only a weak correlation. Our model includes multiple kinases, apoptosis related and zinc ion binding genes. Pathway analysis using the Molecular Signatures Database revealed relevant gene sets (BAF57, Van 't Veer). Next, miRNA profiling was performed on 82/96 tumors using Human MiRNA microarray chips (Illumina). Eight miRNAs were significantly differentially expressed according to lymph node status at a significance level of 0.05, without correcting for multiple testing. The analysis of the inverse correlation between a miRNA and its computationally predicted targets point to general deregulation of the miRNA machinery potentially responsible for lymph node invasion. In conclusion, our results provide evidence that lymph node involvement in breast cancer is not a random process. Gene expression profiling: A training set of 96 patients and an independent internal dataset of 20 patients balanced for lymph node involvement was selected from the multidisciplinary breast centre database miRNA profiling not provided in this Series.
| S-ECPF-GEOD-23177 | biostudies-other
Project description:Gemcitabine (G) and docetaxel (D) are commonly used to treat recurrent/metastatic soft tissue sarcoma. This study tested the hypothesis that outcomes would be improved by addition of bevacizumab (B). The initial design was randomized double-blind trial of G + D + B versus G + D + placebo. Due to slow accrual this was modified to single-arm open-label G + D + B. Eligible patients had diagnosis of leiomyosarcoma, pleomorphic undifferentiated sarcoma, pleomorphic liposarcoma, or angiosarcoma. Treatment was B 15?mg/kg on d1, G 900?mg/m(2) on d1 and d8, and D 75?mg/m(2) on d8, q21d. Primary endpoint was progression-free survival (PFS) at 6 months and would be met if ?17 patients were progression-free at 6?m. Secondary endpoints are response rate, PFS at 3?m, overall survival, and toxicity. Of 44 patients enrolled, 35 were treated with GDB and evaluable for safety and efficacy. Median age was 55, 50% male, most ECOG 0. Toxicity is mostly myelosuppression with one deep vein thrombosis and one small bowel perforation possibly related to B. There were 17 partial responses (49%) by RECIST 1.1. Among 35 patients, the number who remained on study and progression-free was 24 at 3?m and 15 at 6?m. 9 withdrew prior to 6?m for reasons other than toxicity or progression. PFS at 6?m was 65% (95% CI: 51-85%). The primary endpoint of 6?m PFS was not met due to censoring of patients who withdrew. However PFS at 3?m (76%) was promising and response rate was higher than expected from G + D.
| S-EPMC4446476 | biostudies-literature
Project description:Purpose:The current multicenter phase II study was conducted to evaluate the efficacy and safety of the combination of docetaxel and gemcitabine as neoadjuvant chemotherapy (NAC) for locally advanced breast cancer. Methods:A total of 98 patients with stage II-III breast cancer were enrolled. The primary endpoint was pathological complete response (pCR) rate of invasive cancer after the completion of the fourth cycle of NAC. The secondary endpoints included response rate (RR), rate of breast-conserving surgery, toxicity, and disease-free survival (DFS). This study is registered with ClinicalTrials.gov (NCT01352494). Results:pCR in the breast and the axillary lymph node was observed in seven of the 98 enrolled patients (7.1%). The overall clinical RR, including partial responses, was 65.3%. Breast-conserving surgery was performed in 75 of the 98 assessable patients (76.5%). Neutropenia was frequent and was observed in 92 of the 98 patients (93.9%), including grade 3 and 4 in 24 patients (24.5%) and 63 patients (64.3%), respectively. Dose reductions were required for 30 of the 92 patients (32.6%). After a median follow-up of 24 months, the overall DFS of the group was 86.7%. Conclusion:The combination of docetaxel and gemcitabine did not improve pCR. However, this regimen has shown potential as a NAC by producing a reasonable rate of breast-conserving surgery and favorable responses in patients with locally advanced breast cancer. The therapeutic efficacy of this regimen will be determined in additional trials to overcome the limitations of the current study.
| S-EPMC5743993 | biostudies-literature