GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    GRB7 -dependent pathways are potential therapeutic targets in triple-negative breast cancer.
    American Association for Cancer Research (AACR) ; 2009
    In:  Cancer Research Vol. 69, No. 2_Supplement ( 2009-01-15), p. 25-
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 69, No. 2_Supplement ( 2009-01-15), p. 25-
    Abstract: Abstract #25 Background: Breast cancer lacking expression of the estrogen and progesterone receptor and overexpression of HER2/neu (ie, "triple-negative” disease) accounts for about 10-15% of all breast cancer and is characterized by a higher risk of recurrence, early recurrence, resistance to cytotoxic therapy, and lack of any specific targeted therapy. & #x2028; Methods: We extracted RNA from primary tumor samples of 246 patients with stage I-III triple-negative breast cancer (confirmed in a central lab) treated with 4 cycles of adjuvant doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) or docetaxel (60 mg/m2) who were enrolled on trial E2197, and correlated RNA expression (by quantitative RT-PCR using a panel of 371 rationally selected genes) with recurrence. There was no difference in recurrence between the two treatment arms in the entire study population, nor in the 246 patients in this analysis (of whom 59 recurred) after a median followup of 76 months. & #x2028; Results: Higher expression of GRB7 was the only gene significantly associated with an increased risk of recurrence (nominal p value 0.0000853, Korn's adjusted p value controlling false discovery at 10% (KP10) p=0.0359), but did not correlate with any clinicopathologic features except age (low expression associated with age & gt; 65 years, p=0.03). In a Cox proportional hazards model adjusted for age, nodal status, tumor size, and grade, higher GRB7 expression was associated with an increased risk of recurrence when evaluated as a continuous variable (hazard ratio 3.41; p = 0.001) or as a dichotomous variable (hazard ratio 2.24 above vs. below median; p=0.006). The 5-year recurrence rates were 10.5% (95% C.I.7.8%, 14.1%) in the low and 20.4% (95% C.I. 16.5%, 25.0%) in the high GRB7 groups. There were only six genes whose expression correlated with GRB7 (r & gt; 0.4), including ERBB2 (r=0.70), DDR1 (discoidin domain receptor tyrosine kinase 1; r=0.53), KRT19 (keratin 19; r=0.49), ERBB3 (r=0.48), GPR56 (G protein-coupled receptor 56; r=0.48) and PHB (prohibitin; r=0.42). & #x2028; Conclusions: GRB7 is a calmodulin-binding protein which has an SH2 (Src homology 2) domain that binds to phosphorylated tyrosine residues and other specific protein targets, and which plays a critical role in signaling (EGFR, HER2), motility (eprhins), migration (focal adhesion kinase), and cell-matrix/cell-cell interactions (integrins). Higher GRB7 RNA expression is associated with a significantly higher risk of recurrence in triple-negative breast cancer, indicating that GRB7 or GRB7-dependent pathways are potential therapeutic targets in triple-negative disease. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 25.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.SABCS-25
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Gene Expression Profiling of Phenotypically-Defined Hormone-Receptor Positive Breast Cancer: Evidence for Increased Transcriptional Activity of the Insulin Growth Factor Receptor Pathway and Other Pathways.
    American Association for Cancer Research (AACR) ; 2009
    In:  Cancer Research Vol. 69, No. 24_Supplement ( 2009-12-15), p. 5165-5165
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 69, No. 24_Supplement ( 2009-12-15), p. 5165-5165
    Abstract: Background: Approximately 70% of all breast cancers are hormone receptor (HR)-positive tumors that are sensitive to endocrine therapy, but some patients have recurrence despite adjuvant endocrine therapy. We performed an exploratory analysis of gene expression in HR-pos operable breast cancer in order to identify potential novel therapeutic targets and biomarkers associated with recurrence. Methods: RNA was extracted from primary tumor samples obtained from 776 patients with stage I-III breast cancer treated with adjuvant chemohormonal therapy in trial E2197 (JCO 2008; 26: 4092-4099), of whom 458 had HR-pos disease (defined in a central lab; JCO 2008; 26: 2473). We evaluated RNA expression patterns (by quantitative RT-PCR using a panel of 371 rationally selected genes) in HR-pos cases compared with the HR-neg cases using weighted T statistics, and determined which genes in the HR-pos, HER2-neg group were associated with recurrence (using Cox proportional hazards model score test, Korn's adjusted P value & lt;5% with false discovery rate & lt; 10%).Results: The top 10 genes exhibiting significantly higher expression in the HR-pos group (p≤ 6.17e-160) included ESR1 plus 5 estrogen regulated genes, confirming our approach of evaluating gene expression in phenotypically-defined subsets. Other pathways that exhibited higher expression in the HR-pos group (among the 40 top genes with higher expression, p & lt;8.66e-53) included the insulin growth factor (IGF) (IRS1, IGFR1, IGFB2), Ras (RhoB, RhoC, RAB27B, GGPS1), and HER pathways (ERBB2, ERBB3, ERBB4), and other genes involved in apoptosis (BCL2, BCL2L1, BAG1, NME6, BBC3), signaling (MAPK3, SEMA3F, RXRA), mismatch repair (MSH3), cell cycle regulation (CCND1), stress response (HSPB1), and tumor suppressor genes (TP53BP1, APC). These patterns were similar in HER2-pos cases. Pathway analysis (Ingenuity) revealed substantial interconnectivity among these genes, especially between IGFR1, ERB2/3/4, MAPK3, BCL2, and CCND1, but not RhoB/RhoC. Genes for which increased expression was associated with increased recurrence included those associated with proliferation (TOP2A, AURKB, PLK1) and apoptosis (BIRC5 - survivin).Conclusions: This exploratory analysis reveals several pathways that exhibit higher transcriptional expression in HR-pos disease, some of which are also associated with a higher risk of recurrence, suggesting that they may be potential therapeutic targets. This provides rationale for testing agents currently available in the clinic that inhibit the IGF and other pathways. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5165.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.SABCS-09-5165
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    HER2 concordance between central laboratory immunohistochemistry and quantitative reverse transcription polymerase chain reaction in Intergroup Trial E2197
    American Society of Clinical Oncology (ASCO) ; 2008
    In:  Journal of Clinical Oncology Vol. 26, No. 15_suppl ( 2008-05-20), p. 22009-22009
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 26, No. 15_suppl ( 2008-05-20), p. 22009-22009
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2008.26.15_suppl.22009
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2008
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Concordance of local and central laboratory hormone and HER2 receptor status in ECOG 2197
    American Society of Clinical Oncology (ASCO) ; 2007
    In:  Journal of Clinical Oncology Vol. 25, No. 18_suppl ( 2007-06-20), p. 21022-21022
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 18_suppl ( 2007-06-20), p. 21022-21022
    Abstract: 21022 Background: Central and local laboratory concordance for hormone and HER2 receptor measurement is of national interest. This study compares ER/PR/HER2 by local laboratories using immunohistochemistry (IHC) and central laboratories (IHC & quantitative RT-PCR). Methods: Of 2952 patients in E2197, a case-cohort sample of 776 patients who either did (N=179) or did not recur was studied. Central IHC for ER/PR/HER2 was performed using single 0.6 mm microarrays; Allred score (AS) was used for ER/PR (AS 〉 2 = positive). Positive HER2 was 3+ staining in 〉 10% cells for Central IHC and 2+ or 3+ for Local IHC. RT-PCR analysis by Oncotype DX™ for ER/PR/HER2 was performed using pre-defined cutoffs of 6.5, 5.5 and 11.5 units, respectively. Hormone receptor (HR) pos was defined as ER & /or PR pos. Results: Results from Local IHC (ER/PR in 776 & HER2 in 517 pts) were compared with Central IHC (760 pts) and RT-PCR results (776 pts). The discordance between HR positivity by Local IHC and RT-PCR was very low. However, 12% of HR neg pts by Local IHC (38/321) & Central IHC (39/326) were HR pos by RT-PCR. The relationship between ER and recurrence as a function of AS was examined. Patients with AS of 3–4 were found to be closer to the AS=2 group than to the AS 〉 4 group Patients with AS of 3–4 were found to be closer to the AS ÿ 2 group than to the AS 〉 4 group (Est.HR for ER 0.97 for AS 3–4 vs. 0–2 and 0.46 for AS 5–8 vs. 0–2, and for PR were 0.84 for AS 3–4 vs. 0–2 and 0.41 for AS 5–8 vs. 0–2). Conclusions: There is a high degree of overall concordance among Local IHC, Central IHC, and Central RT-PCR for ER and PR. The degree of concordance is even greater for HR compared to ER or PR alone. Although the concordance with local labs for HER2 testing was poor, the concordance between Central IHC and RT-PCR was very high. The relatively high incidence (12%) of IHC HR neg pts who are HR pos by RT- PCR is notable. [Table: see text] [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2007.25.18_suppl.21022
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2007
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Abstract Submission
    American Society of Clinical Oncology (ASCO) ; 2007
    In:  Journal of Clinical Oncology Vol. 25, No. 18_suppl ( 2007-06-20), p. 526-526
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 18_suppl ( 2007-06-20), p. 526-526
    Abstract: 526 Background: Evidence suggests modern chemotherapy (CT) regimens are only marginally more effective in HR-pos breast cancer (Berry et al. JAMA 2006: 295: 1658). Genomic classifiers may be useful for selection of high-risk subjects for more aggressive CHT. Methods: A case-cohort sample of 776 patients enrolled on E2197 who did (N=179) or did not have a recurrence after CT (if HR-neg) or CHT (if HR-pos) and had available tissue were evaluated for Oncotype DX™ Recurrence Score (RS). E2197 included 2885 evaluable patients with 0–3 positive nodes treated with four 3-week cycles of doxorubicin (60 mg/m 2 ) plus cyclophosphamide 600 mg/m 2 (AC) or docetaxel 60 mg/m 2 (AT) and hormonal therapy (if HR-pos). Median follow-up was 76 months. Results: There was no difference in DFS between treatment arms. In multivariate analysis, RS was a significant predictor of recurrence in HR-pos disease (p=0.0007, recurrence risk 21% lower for each 10 point drop in RS, 95% confidence intervals 9% to 31%). Recurrence risk was significantly elevated for an intermediate RS 18–30 (n=138, hazard ratio [HR] 2.96 [p=0.0002] ) or a high RS ≥ 31 (n=108, HR 4.00, p=0.0001) compared with low RS 〈 18(n=196), but not for high compared with intermediate RS (HR 1.34, [p=0.32]); results were similar if only HER2-neg disease was included. The 5-year relapse free interval(RFI), breast cancer free survival (BCFS), disease-free survival (DFS), and overall survival (OS) for patients with HR-pos, HER2-neg disease are shown below (%); patients with both node-neg or node-pos breast cancers whose RS was 〈 18 had excellent outcomes. Conclusions: Oncotype DX™ RS identifies individuals with HR-pos, HER2-neg breast cancer with 0–3 positive axillary lymph nodes at 3–4-fold increased risk of relapse despite standard CHT, and may serve as a means to distinguish between those who do well with standard CHT (RS 〈 18) from those who may be suitable candidates for clinical trials evaluating alternative CT regimens or other strategies (RS ≥ 18). [Table: see text] [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2007.25.18_suppl.526
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2007
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Predictive utility of progesterone receptor (PR) and multigene expression in identifying benefit from adjuvant doxorubicin plus cyclophosphamide (AC) or docetaxel (AT) in intergroup trial E2197
    American Society of Clinical Oncology (ASCO) ; 2008
    In:  Journal of Clinical Oncology Vol. 26, No. 15_suppl ( 2008-05-20), p. 557-557
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 26, No. 15_suppl ( 2008-05-20), p. 557-557
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2008.26.15_suppl.557
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2008
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Expression of the 21 genes in the Recurrence Score assay and tamoxifen clinical benefit in the NSABP study B-14 of node negative, estrogen receptor positive breast cancer
    American Society of Clinical Oncology (ASCO) ; 2005
    In:  Journal of Clinical Oncology Vol. 23, No. 16_suppl ( 2005-06), p. 510-510
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 23, No. 16_suppl ( 2005-06), p. 510-510
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2005.23.16_suppl.510
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2005
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Gene expression profiles in formalin-fixed, paraffin-embedded (FFPE) core biopsies predict docetaxel chemosensitivity
    American Society of Clinical Oncology (ASCO) ; 2006
    In:  Journal of Clinical Oncology Vol. 24, No. 18_suppl ( 2006-06-20), p. 538-538
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 24, No. 18_suppl ( 2006-06-20), p. 538-538
    Abstract: 538 Background: Docetaxel has one of the highest response rates as a single agent in breast cancer, but de novo resistance is frequent. Previously, we had identified a 92-gene expression pattern that predicted response to neoadjuvant docetaxel. Other studies have validated that a high Recurrence Score (RS) by the 21-gene RT-PCR assay is predictive of worse prognosis (Paik, NEJM 2004) but better response to chemotherapy (Gianni, JCO 2005). We investigated whether tumor gene expression of these 21 genes and other candidate genes can predict response to docetaxel. Methods: Core biopsies from 97 patients were obtained before treatment with neoadjuvant docetaxel (4 cycles, 100 mg/m 2 q3 weeks). Baseline and post-treatment measurements of the primary breast cancers were recorded. Three 10-micron FFPE sections were submitted for quantitative RT-PCR assays of 192 genes that were selected from our previous work and the literature. Results: Of the 97 patients, 81 (84%) had sufficient invasive breast cancer, 80 (82%) had sufficient RNA for assay of 192 genes, and 72 (74%) had clinical response data. Mean age was 48.5 years, and the median tumor size was 6 cm. Clinical complete responses (CR) by RECIST were observed in 12 (17%), partial responses in 41 (57%), stable disease in 17 (24%), and progressive disease in 2 patients (3%). The concordance of IHC and RT-PCR results was 〉 80% for ER, PgR, and HER2. By univariate logistic regression, a significant correlation (p 〈 0.05) between gene expression and CR was observed for 14 genes. Notably, CYBA-1 involved in mitochondrial metabolism, identified by gene expression profiling, significantly predicted CR (p=0.006). CR was associated with lower expression of the ER gene group and higher expression of the proliferation gene group. Multivariate analysis indicated that panels of genes better predictors of docetaxel response. Of note, CR was more likely with high RS and less likely with a low RS (p=0.008). Conclusion: We have established molecular profiles for breast cancers either responding or not responding to neoadjuvant docetaxel. This technology is a potential predictive test for docetaxel sensitivity by using small amounts of FFPE material, and may reduce unnecessary treatment, toxicity, and cost for breast cancer patients. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2006.24.18_suppl.538
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2006
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Evaluation of tumor gene expression and K-Ras mutations in FFPE tumor tissue as predictors of response to cetuximab in metastatic colorectal cancer
    American Society of Clinical Oncology (ASCO) ; 2008
    In:  Journal of Clinical Oncology Vol. 26, No. 15_suppl ( 2008-05-20), p. 3512-3512
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 26, No. 15_suppl ( 2008-05-20), p. 3512-3512
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2008.26.15_suppl.3512
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2008
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Genotypic characterization of phenotypically defined triple-negative breast cancer
    American Society of Clinical Oncology (ASCO) ; 2009
    In:  Journal of Clinical Oncology Vol. 27, No. 15_suppl ( 2009-05-20), p. 500-500
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 27, No. 15_suppl ( 2009-05-20), p. 500-500
    Abstract: 500 Background: Triple negative breast cancer (TNBC) is associated with a higher risk of recurrence and earlier recurrences than other breast cancer phenotypes. We evaluated the genotypic features of TNBC compared with hormone receptor (HR)-positive disease, and also evaluated genotypic features associated with recurrence. Methods: RNA extracted from tumor samples obtained from 764 patients with stage I-III breast cancer was analyzed by RT-PCR for 371 genes. All patients received adjuvant chemotherapy (plus hormonal therapy in HR-positive disease) in trial E2197; HR and HER2 expression were evaluated by immunohistochemistry (IHC) in a central lab (J Clin Oncol 26:2473–2481). An unsupervised clustering analysis was performed in all samples (N=764). Cox proportional hazard models were used to identify differences in gene expression in TNBC versus HR-positive disease, and with recurrence in phenotypically defined (by IHC) TNBC (N=246) and HR-positive (N=465) disease. Results: Unsupervised analysis revealed two major clusters that differed with regard to HR expression by IHC. Supervised analysis comparing the TNBC vs. HR-positive phenotypes revealed 269 genes (73%) with significantly different expression (p 〈 0.0001). The top 10% of genes exhibiting higher expression the TN group included genes associated with nucleosome assembly (CENPA), kinase activity (TTK), cell division (KIFC2), proliferation (BUB1), intracellular signaling (DEPDC1), DNA repair (CHK1), anti-apoptosis (GSTP1), and transcriptional regulation (MYBL2). There was increased expression of genes for which inhibitors are currently being evaluated, including AURKB and CHK1 in TNBC, and IGF1R and RhoC in HR-positive disease. Although GRB7 expression was significantly lower in the TN group, increased expression of GRB7 was the only gene in the TNBC group (but not the HR-positive group) associated with increased recurrence (p=0.04), and did not correlate with nodal status, tumor size, or grade. Conclusions: We genotypically characterized breast cancers that have also undergone rigorous phenotypic characterization.. There were significant differences in gene expression between the TN and HR-positive groups, including genes for which targeted agents are currently being evaluated in the clinic. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2009.27.15_suppl.500
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2009
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...