Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA265806 | ENA |
REPOSITORIES: ENA
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Project description:Development and validation of a predictive algorithm for the degree of benefit from adjuvant trastuzumab: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-31
| PRJNA265805 | ENA
Project description:<p><b><u>Background</u></b><br/> National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31 suggested the efficacy of adjuvant trastuzumab, even in HER2-negative breast cancer. This finding prompted us to develop a predictive model for degree of benefit from trastuzumab using archived tumor blocks from B-31. </p> <p><b><u>Methods</u></b><br/> Case subjects with tumor blocks were randomly divided into discovery (n = 588) and confirmation cohorts (n = 991). A predictive model was built from the discovery cohort through gene expression profiling of 462 genes with nCounter assay. A predefined cut point for the predictive model was tested in the confirmation cohort. Gene-by-treatment interaction was tested with Cox models, and correlations between variables were assessed with Spearman correlation. Principal component analysis was performed on the final set of selected genes. All statistical tests were two-sided. </p> <p><b><u>Results</u></b><br/> Eight predictive genes associated with HER2 (ERBB2, c17orf37, GRB7) or ER (ESR1, NAT1, GATA3, CA12, IGF1R) were selected for model building. Three-dimensional subset treatment effect pattern plot using two principal components of these genes was used to identify a subset with no benefit from trastuzumab, characterized by intermediate-level ERBB2 and high-level ESR1 mRNA expression. In the confirmation set, the predefined cut points for this model classified patients into three subsets with differential benefit from trastuzumab with hazard ratios of 1.58 (95% confidence interval [CI] = 0.67 to 3.69; P = .29; n = 100), 0.60 (95% CI = 0.41 to 0.89; P = .01; n = 449), and 0.28 (95% CI = 0.20 to 0.41; P < .001; n = 442; P interaction between the model and trastuzumab < .001). </p> <p><b><u>Conclusions</u></b><br/> We developed a gene expression-based predictive model for degree of benefit from trastuzumab and demostrated that HER2-negative tumors belong to the moderate benefit group, thus providing justification for testing trastuzumab in HER2-negative patients (NSABP B-47).</p> <p>** Reprinted from J Natl Cancer Inst;2013;105:1782-1788 with permission from Oxford University Press.</p>
| phs000826 | dbGaP
Project description:Gene expression profiling of invasive breast cancer events from the tamoxifen prevention trial validates low estrogen receptor mRNA level as the main determinant of tamoxifen resistance in estrogen receptor positive breast cancer. In NSABP Breast Cancer Prevention Trial (BCPT), tamoxifen reduced the incidence of estrogen receptor (ER) positive tumors but not estrogen receptor negative breast cancer. More importantly, only 69% of estrogen receptor positive tumors were prevented by tamoxifen. The ER positive tumors arising in tamoxifen arm provides an ideal clinical model for acquired tamoxifen resistance. Based on data from NSABP trial B14 which showed linear prediction of the degree of benefit from adjuvant tamoxifen by the levels of ESR1 mRNA coding for ER-alpha, we hypothesized a priori that level of ESR1 mRNA would be lower in ER positive tumors arising in tamoxifen arm compared to those in placebo arm of BCPT. Keywords: Gene expression profiling analysis
2011-12-08 | GSE12665 | GEO
Project description:The clinical relevance of tumor infiltrating lymphocytes (TILs) in breast cancer (BC) is not firmly established. We aimed to validate previous prognostic findings in triple negative breast cancer (TNBC) and investigate predictive associations with trastuzumab benefit in HER2 overexpressing disease (HER2+).
2022-07-16 | GSE47994 | GEO
Project description:Gene expression profiling of invasive breast cancer events from the tamoxifen prevention trial validates low estrogen receptor mRNA level as the main determinant of tamoxifen resistance in estrogen receptor positive breast cancer. In NSABP Breast Cancer Prevention Trial (BCPT), tamoxifen reduced the incidence of estrogen receptor (ER) positive tumors but not estrogen receptor negative breast cancer. More importantly, only 69% of estrogen receptor positive tumors were prevented by tamoxifen. The ER positive tumors arising in tamoxifen arm provides an ideal clinical model for acquired tamoxifen resistance. Based on data from NSABP trial B14 which showed linear prediction of the degree of benefit from adjuvant tamoxifen by the levels of ESR1 mRNA coding for ER-alpha, we hypothesized a priori that level of ESR1 mRNA would be lower in ER positive tumors arising in tamoxifen arm compared to those in placebo arm of BCPT. Keywords: Gene expression profiling analysis Formalin fixed paraffin embedded tumor blocks with enough tumor tissue for RNA extraction were available from 108 cases (69 from placebo arm and 39 from tamoxifen arm) of the 264 that experienced invasive breast cancer (175 in placebo arm and 89 in tamoxifen arm) in BCPT before unblindings . Central ER immunohistochemistry identified 84 of them as ER positive (57 from placebo arm and 27 from tamoxifen arm). A novel protocol was developed and used to obtain microarray gene expression profiling from the degraded or fragmented RNA extracted from formalin fixed paraffin blocks.Hybridization intensity data were compiled using Partek Genomic Suite. After quantile normalization, genes with mean intensity below 500 were filtred out, which left 7743 probes with informative data. Data were log2 transformed for statistical analysis.
2011-12-08 | E-GEOD-12665 | biostudies-arrayexpress
Project description:The human epidermal growth factor receptor 2 (HER2) gene encodes a tyrosine kinase receptor that controls important signal transduction pathways in breast cancer. Amplification and overexpression of the HER2 gene occurs in approximately 20% of breast cancers and is associated with an aggressive clinical phenotype. Trastuzumab, a humanized monoclonal antibody that targets HER2 showed exceptional efficacy in the treatment of breast cancer. In the adjuvant treatment of breast cancer patients, five randomized trials showed significant benefit of trastuzumab, with a reduction in the rate of recurrence of approximately 50% and improvement in the rate of survival of approximately 30%. In the current study, positive early stage breast cancer samples treated with adjuvant trastuzumab provided by institute Jules Bordet (IJB) and KUL. Gene expression and clinical outcome data were available. to better understand the genetic regulations and effects of the trastuzumab, we profile the the genes expression of positive early stage breast cancer samples treated with adjuvant trastuzumab.
2016-12-31 | GSE58984 | GEO
Project description:Trastuzumab, a humanized monoclonal antibody directed to the HER2 protein, is the standard-of-care treatment for patients with HER2 positive breast cancer, reducing the risk of relapse and death in patients. Nonetheless, some patients relapse after treatment, underscoring the need to identify patients for whom chemotherapy + trastuzumab is adequate versus patients requiring additional drugs. To search for genes predictive of relapse in HER2-positive breast carcinoma patients treated with adjuvant trastuzumab, we conducted gene expression profiling analysis in 53 cases treated in the clinic with doxorubicin/paclitaxel (AT) followed by cyclophosphamide/methotrexate/fluorouracil (CMF) and trastuzumab.
2015-10-19 | GSE55348 | GEO
Project description:Adjuvant docetaxel, carboplatin, and trastuzumab (TCH) is a standard regimen for HER2+ breast cancer. Dual HER2-blockade with lapatinib (L) and trastuzumab demonstrated significant activity in the metastatic and neoadjuvant settings. This study evaluates neoadjuvant TC plus trastuzumab (H) and/or lapatinib (L). This study demonstrated a similar pCR rate with TCH and TCHL and a lower rate of pCR with TCL. Treatment-related toxicity limited the ability for participants to receive protocol-specified chemotherapy and HER2-targeted therapy in the TCHL Arm.
2019-05-08 | GSE130787 | GEO
Project description:Adjuvant docetaxel, carboplatin, and trastuzumab (TCH) is a standard regimen for HER2+ breast cancer. Dual HER2-blockade with lapatinib (L) and trastuzumab demonstrated significant activity in the metastatic and neoadjuvant settings. This study evaluates neoadjuvant TC plus trastuzumab (H) and/or lapatinib (L). This study demonstrated a similar pCR rate with TCH and TCHL and a lower rate of pCR with TCL. Treatment-related toxicity limited the ability for participants to receive protocol-specified chemotherapy and HER2-targeted therapy in the TCHL Arm.
2019-05-08 | GSE130786 | GEO
Project description:Trastuzumab, a humanized monoclonal antibody directed to the HER2 protein, is the standard-of-care treatment for patients with HER2 positive breast cancer, reducing the risk of relapse and death in patients. Nonetheless, some patients relapse after treatment, underscoring the need to identify patients for whom chemotherapy + trastuzumab is adequate versus patients requiring additional drugs. To search for genes predictive of relapse in HER2-positive breast carcinoma patients treated with adjuvant trastuzumab, we conducted gene expression profiling analysis in 53 cases treated in the clinic with doxorubicin/paclitaxel (AT) followed by cyclophosphamide/methotrexate/fluorouracil (CMF) and trastuzumab. Gene expression profiling was performed using RNA from formalin-fixed paraffin-embedded tissues from 53 patients with primary HER2-positive (HER2+) tumors. The series consists in 23 relapsed and 30 non-relapsed cases with similar clinical-pathological characteristics (size, pathological lymph node involvement and estrogen receptor positivity) (3-year median follow up).
2015-10-19 | E-GEOD-55348 | biostudies-arrayexpress