Ontology highlight
ABSTRACT:
PROVIDER: PRJEB28702 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Molecular Determinants of Post-Mastectomy Breast Cancer Recurrence
2018-09-20 | PRJEB28702 | EVA
Project description:Molecular Determinants of Post-Mastectomy Breast Cancer Recurrence
| PRJNA490741 | ENA
Project description:Breast cancer (BC) adjuvant therapy after mastectomy in the setting of 1-3 positive lymph nodes has been controversial. This retrospective Translational Breast Cancer Research Consortium study evaluated molecular aberrations in primary cancers associated with locoregional recurrence (LRR) or distant metastasis (DM) compared to non-recurrent controls. We identified 115 HER2 negative, therapy naïve, T 1-3 and N 0-1 BC patients treated with mastectomy but no post-mastectomy radiotherapy. This included 32 LRR, 34 DM and 49 controls. RNAseq was performed on primary tumors in 110 patients; with no difference in RNA profiles between patients with LRR, DM or controls. DNA analysis on 57 primary tumors (17 LRR, 15 DM and 25 controls) identified significantly more NF1 mutations and mitogen activated protein kinase (MAPK) pathway gene mutations in patients with LRR (24%, 47%) and DM (27%, 40%) compared to controls (0%, 0%; p<0.0001 and p=0.0070, respectively). Three patients had matched primary vs LRR samples, one patient had a gain of a NF1 mutation in the LRR. There was no significant difference between the groups for PTEN loss or cleaved caspase 3 expression. The mean percentage Ki 67 labeling index was higher in patients with LRR (29.2%) and DM (26%) versus controls (14%,p= 0.0045). In summary, mutations in the MAPK pathway, specifically NF1, were associated with both LRR and DM, suggesting that alterations in MAPK signaling are associated with a more aggressive tumor phenotype. Validation of these associations in tissues from randomized trials may support targeted therapy to reduce breast cancer recurrence.
2018-09-14 | GSE119937 | GEO
Project description:Introduction: Overall survival of early-stage breast cancer (BC) patients is similar for those who undergo breast conserving therapy (BCT) and mastectomy, however, 10-15% of women undergoing BCT suffer ipsilateral breast tumor recurrence. The risk of recurrence may vary with age or breast cancer subtype. Understanding the gene expression of the cancer-adjacent tissue and/or stromal response to specific tumor subtypes is important for developing clinical strategies to reduce recurrence risk. Methods: We studied gene expression data in cancer-adjacent tissue from 158 BC patients. Complementary in vitro cocultures were used to study cell-cell communication between fibroblasts and specific breast cancer subtypes. Results: Our results suggest that intrinsic tumor subtypes are reflected in histologically normal cancer-adjacent tissue. Gene expression of cancer-adjacent tissues shows that triple negative (Claudin-low or Basal-like tumors) exhibit increased expression of genes involved in inflammation and immune response. While such changes could reflect distinct immune populations present in the microenvironment of different breast cancer subtypes, altered immune response gene expression was also observed in cocultures in the absence of immune cell infiltrates, emphasizing that these inflammatory mediators are secreted by breast-specific cells. In addition, while triple negative BCs are associated with upregulated immune response genes, Luminal breast cancers are more commonly associated with estrogen-response in adjacent tissues. Conclusions: Specific characteristics of BCs are reflected in the surrounding benign tissue. This commonality between tumor and surrounding tissue may underlie second primaries and local recurrences. Biomarkers derived from cancer-adjacent tissue may be helpful in defining personalized surgical strategies or in predicting recurrence risk. reference x sample
2014-04-30 | E-GEOD-50939 | biostudies-arrayexpress
Project description:Breast cancer molecular subtypes preferentially metastasize to specific organs and the anatomical location of the metastasis is associated with the length of survival post-recurrence. We used microarrays to provide a detailed characterization of breast cancer site-specific metastases with particular focus on identifying genes predictive of breast cancer liver metastatic proprnsity
2013-12-02 | GSE46141 | GEO
Project description:Introduction: Overall survival of early-stage breast cancer (BC) patients is similar for those who undergo breast conserving therapy (BCT) and mastectomy, however, 10-15% of women undergoing BCT suffer ipsilateral breast tumor recurrence. The risk of recurrence may vary with age or breast cancer subtype. Understanding the gene expression of the cancer-adjacent tissue and/or stromal response to specific tumor subtypes is important for developing clinical strategies to reduce recurrence risk. Methods: We studied gene expression data in cancer-adjacent tissue from 158 BC patients. Complementary in vitro cocultures were used to study cell-cell communication between fibroblasts and specific breast cancer subtypes. Results: Our results suggest that intrinsic tumor subtypes are reflected in histologically normal cancer-adjacent tissue. Gene expression of cancer-adjacent tissues shows that triple negative (Claudin-low or Basal-like tumors) exhibit increased expression of genes involved in inflammation and immune response. While such changes could reflect distinct immune populations present in the microenvironment of different breast cancer subtypes, altered immune response gene expression was also observed in cocultures in the absence of immune cell infiltrates, emphasizing that these inflammatory mediators are secreted by breast-specific cells. In addition, while triple negative BCs are associated with upregulated immune response genes, Luminal breast cancers are more commonly associated with estrogen-response in adjacent tissues. Conclusions: Specific characteristics of BCs are reflected in the surrounding benign tissue. This commonality between tumor and surrounding tissue may underlie second primaries and local recurrences. Biomarkers derived from cancer-adjacent tissue may be helpful in defining personalized surgical strategies or in predicting recurrence risk.
2014-04-30 | GSE50939 | GEO
Project description:Basal-like breast cancer (BBC) is an aggressive subtype of breast cancer that has no biologically targeted therapy. The interactions of BBCs with stromal cells are important determinants of tumor biology, with inflammatory cells playing well-recognized roles in cancer progression. Despite the fact that macrophage–BBC communication is bidirectional, important questions remain about how BBCs affect adjacent immune cells. This study investigated monocyte-to-macrophage differentiation and polarization and gene expression in response to coculture with basal like versus luminal breast cancer cells. Changes induced by coculture were compared with changes observed under classical differentiation and polarization conditions. Monocytes (THP-1 cells) exposed to BBC cells in coculture had altered gene expression with upregulation of both M1 and M2 macrophage markers. Two sets of M1 and M2 markers were selected from the PCR profiles and used for dual immunofluorescent staining of BBC versus luminal cocultured THP-1s, and cancer-adjacent, benign tissue sections from patients diagnosed with BBCs or luminal breast cancer, confirming the differential expression patterns. Relative to luminal breast cancers, BBCs also increased differentiation of monocytes to macrophages and stimulated macrophage migration. Consistent with these changes in cellular phenotype, a distinct pattern of cytokine secretion was evident in macrophage–BBC cocultures, including upregulation of NAP-2, osteoprotegerin, MIG, MCP-1, MCP-3, and interleukin (IL)-1b. Application of IL-1 receptor antagonist (IL-1RA) to cocultures attenuated BBC-induced macrophage migration. These data contribute to an understanding of the BBC-mediated activation of the stromal immune response, implicating specific cytokines that are differentially expressed in basal-like microenvironments and suggesting plausible targets for modulating immune responses to BBCs.Introduction: Overall survival of early-stage breast cancer (BC) patients is similar for those who undergo breast conserving therapy (BCT) and mastectomy, however, 10-15% of women undergoing BCT suffer ipsilateral breast tumor recurrence. The risk of recurrence may vary with age or breast cancer subtype. Understanding the gene expression of the cancer-adjacent tissue and/or stromal response to specific tumor subtypes is important for developing clinical strategies to reduce recurrence risk. Methods: We studied gene expression data in cancer-adjacent tissue from 158 BC patients. Complementary in vitro cocultures were used to study cell-cell communication between fibroblasts and specific breast cancer subtypes. Results: Our results suggest that intrinsic tumor subtypes are reflected in histologically normal cancer-adjacent tissue. Gene expression of cancer-adjacent tissues shows that triple negative (Claudin-low or Basal-like tumors) exhibit increased expression of genes involved in inflammation and immune response. While such changes could reflect distinct immune populations present in the microenvironment of different breast cancer subtypes, altered immune response gene expression was also observed in cocultures in the absence of immune cell infiltrates, emphasizing that these inflammatory mediators are secreted by breast-specific cells. In addition, while triple negative BCs are associated with upregulated immune response genes, Luminal breast cancers are more commonly associated with estrogen-response in adjacent tissues. Conclusions: Specific characteristics of BCs are reflected in the surrounding benign tissue. This commonality between tumor and surrounding tissue may underlie second primaries and local recurrences. Biomarkers derived from cancer-adjacent tissue may be helpful in defining personalized surgical strategies or in predicting recurrence risk. reference x sample
2013-11-15 | E-GEOD-52292 | biostudies-arrayexpress
Project description:Breast cancer molecular subtypes preferentially metastasize to specific organs and the anatomical location of the metastasis is associated with the length of survival post-recurrence. We used microarrays to provide a detailed characterization of breast cancer site-specific metastases with particular focus on identifying genes predictive of breast cancer liver metastatic proprnsity We performed global gene expression profiling on fine-needle aspirates of metastatic lesions from different anatomical sites obtained from breast cancer patients treated within the Swedish randomized trial (TEX) of first-line chemotherapy for locally advanced or metastatic breast cancer. Samples were collected before commencement of treatment.
2013-12-02 | E-GEOD-46141 | biostudies-arrayexpress
Project description:Transcriptome profiles of MDA-MB-231 breast cancer cells cultured with interstitial fluids from post-mastectomy breast cancer patients
| PRJNA311611 | ENA
Project description:A "Cartes d'Identite des Tumeurs" (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net). 37 samples hybridized on Affymetrix HG-U133A arrays. Analysis of advanced breast cancers treated with a dose-intense epirubicin /cyclophosphamide regimen followed by mastectomy; Validation of TP53-related genes in breast and bladder cancers. We found that a complete response to chemotherapy was only observed in TP53 mutant tumours. We further show that, among TP53 mutant tumours, high basalcytokeratin and low ESR1 expression levels were associated with complete responses. These observations pave the way to molecular tailoring of chemotherapy in breast cancer.
2007-03-26 | E-TABM-43 | biostudies-arrayexpress