Whole transcriptome analysis comparing HR+ HER2- breast cancer tumors from patients 50 years.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 565-565
Author(s):  
Cathy Graham ◽  
Douglas Kanter Marks ◽  
Nina D'Abreo ◽  
Sami Diab ◽  
Vijayakrishna K. Gadi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcriptome Analysis ◽  
Gene Signature ◽  
Low Risk ◽  
Chemotherapy Response ◽  
Luminal B ◽  
Whole Transcriptome Analysis ◽  
Post Menopausal ◽  
Whole Transcriptome ◽  
Basal Type

565 Background: Recent prospective clinical trials have demonstrated a differential chemotherapy effect based on age (≤ 50 vs. > 50 years) or menopausal status (pre- vs. post-) in a genomic low risk group. Whether this is a direct anti-tumor effect of chemotherapy or a secondary ovarian function suppression effect caused by chemotherapy is unclear. We aimed to compare the biological characteristics of breast cancer tumors from patients aged ≤ 50 years and from patients aged > 50 years using whole transcriptome analysis to provide insights into this differential chemotherapy response. Methods: The FLEX Registry (NCT03053193) enrolls stage I-III breast cancer patients who receive 70-gene signature (MammaPrint/MP) test with or without 80-gene signature (BluePrint/BP) test and consent to clinically annotated transcriptome data collection. 3868 patients with HR+HER2- tumors were evaluated, of whom 808 were aged ≤ 50 years and 3060 were aged > 50 years. Clinical risk was assessed based on the MINDACT algorithm. MP classified tumors as low risk (LR) or high risk (HR). HR was stratified to H1 or H2; H2 exhibits a greater chemotherapy response. BP and MP classified tumors as luminal A-, luminal B-, HER2-, or basal-type. Differences in MP, BP, and clinical features were assessed by chi-squared or t test. For gene expression analysis, older patients were randomly selected to obtain an equal sample size as younger patients. Differentially expressed genes (DEGs) were detected using limma and considered significant with FDR <0.05 and fold change ≥ 2. Results: Approximately 70% of patients aged ≤ 50 were pre or peri-menopausal, whereas 90% of patients aged > 50 were post-menopausal. A higher proportion of patients aged ≤ 50 had tumors of high clinical risk (54%) compared to patients aged > 50 (39%) (p < 0.001). Approximately 53% of patients aged ≤ 50 had a HR tumor, of whom 25% classified as H2, while patients aged > 50 had a lower frequency (44%) of HR tumors (p<0.001). Additionally, younger patients had more tumors that classified as BP Luminal B and Basal-type than older patients (p<0.001). Principal component analysis of the top 500 genes with the highest variance revealed no distinct clustering by age group. Accordingly, only 5 DEGs were detected in tumors from patients aged ≤ 50 compared to patients aged > 50, and even fewer DEGs were detected when adjusting for MP risk and BP subtype group. Conclusions: Whole transcriptome analysis identified no substantial differences in gene expression between tumors, including Low Risk Luminal-type tumors, from women aged ≤ 50 (mostly pre or peri-menopausal) and women aged > 50 (mostly post-menopausal). These data support the likely explanation that the observed age-dependent difference in chemotherapy benefit in women ≤ 50 or >50 years of age is not due to intrinsic biological differences in breast cancers due to age, but rather to differences in the effect of chemotherapy on the host. Clinical trial information: NCT03053193.

Co-culture of functionally enriched cancer stem-like cells and cancer-associated fibroblasts for single-cell whole transcriptome analysis

2019 ◽  
Vol 11 (9) ◽  
pp. 353-361 ◽  
Author(s):  
Yu-Chih Chen ◽  
Seungwon Jung ◽  
Zhixiong Zhang ◽  
Max S Wicha ◽  
Euisik Yoon
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Transcriptome Analysis ◽  
Stromal Cells ◽  
Transcriptome Sequencing ◽  
Functional Enrichment ◽  
Cancer Associated Fibroblasts ◽  
Tumor Initiation ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome

Abstract Considerable evidence suggests that breast cancer development and metastasis are driven by cancer stem-like cells (CSCs). Due to their unique role in tumor initiation, the interaction between CSCs and stromal cells is especially critical. In this work, we developed a platform to reliably isolate single cells in suspension and grow single-cell-derived spheres for functional enrichment of CSCs. The platform also allows adherent culture of stromal cells for cancer-stromal interaction. As a proof of concept, we grew SUM149 breast cancer cells and successfully formed single-cell-derived spheres. Cancer-associated fibroblasts (CAFs) as stromal cells were found to significantly enhance the formation and growth of cancer spheres, indicating elevated tumor-initiation potential. After on-chip culture for 14 days, we retrieved single-cell derived spheres with and without CAF co-culture for single-cell transcriptome sequencing. Whole transcriptome analysis highlights that CAF co-culture can boost cancer stemness especially ALDHhigh CSCs and alter epithelial/mesenchymal status. Single-cell resolution allows identification of individual CSCs and investigation of cancer cellular heterogeneity. Incorporating whole transcriptome sequencing data with public patient database, we discovered novel genes associated with cancer-CAF interaction and critical to patient survival. The preliminary works demonstrated a reliable platform for enrichment of CSCs and studies of cancer-stromal interaction.

Response and long-term outcomes after neoadjuvant chemotherapy: Pooled dataset of patients stratified by molecular subtyping by MammaPrint and BluePrint.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 10-10
Author(s):  
Stefan Gluck ◽  
Femke De Snoo ◽  
Justine Peeters ◽  
George Somlo ◽  
Lisette Stork-Sloots ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Biomarker Discovery ◽  
Chemotherapy Response ◽  
Long Term Outcomes ◽  
Luminal A ◽  
Molecular Subtyping ◽  
Luminal B ◽  
Luminal Type ◽  
Basal Type

10 Background: Classification of breast cancers into molecular subtypes may be important for the proper selection of therapy for patients with early breast cancer. Previous analyses had shown that breast cancer subtypes have distinct clinical outcome (Sorlie, PNAS, 2001; Esserman, BCRT, 2011). Herein, we analyze using MammaPrint together with an 80-gene molecular subtyping profile (BluePrint) the response to neo-adjuvant chemotherapy and long term outcomes. Methods: This study was carried out on data from 144 patients from the I-SPY I trial; 232 patients from biomarker discovery program at MD Anderson (133 and 99 respectively; Hess, 2006, JCO; Iwamoto, 2011, BCRT); and 68 patients from City of Hope (Somlo, ASCO, 2010). All patients were treated in the neo-adjuvant setting with standard chemotherapy. MammaPrint and BluePrint were determined on 44K Agilent arrays run at Agendia or available through the I-SPY 1 data portal, or from Affymetrix U133A arrays. MammaPrint and BluePrint resulted in 4 distinct molecular groups: Luminal A (MammaPrint Low-risk/Luminal-type), Luminal B (MammaPrint High-risk/Luminal-type), Basal-type and HER2-type. Results: The overall pCR of this patient cohort was 22% but differed substantially among the subgroups. pCR was observed in 5% of the Luminal-A samples and 10% of Luminal-B, in 39% of the HER2-type samples and in 33% of the Basal-type samples. Patients with Basal-type tumors had a 5-year DFS of 71%; HER2-type had a 5-year DFS of 67% (n=71); 69% in HER2-type subgroup not treated with HER2-targeted therapy (n=45); Luminal-B type had a 5-year DFS of 77% and Luminal-A type showed 5-year DFS of 95%. Conclusions: We observed marked differences in response and DFS to neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint. These findings confirm differences in chemotherapy response among molecular subgroups and indicate that the BluePrint and MP profile used for this analysis helps to further establish a clinical correlation between molecular subtyping and treatment outcomes.

Response and long-term outcomes after neoadjuvant chemotherapy: Pooled dataset of patients stratified by molecular subtyping by MammaPrint and BluePrint.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10597-10597
Author(s):  
Stefan Gluck ◽  
Femke De Snoo ◽  
Justine Peeters ◽  
George Somlo ◽  
Laura Van T Veer
Keyword(s):  
Breast Cancer ◽  
Biomarker Discovery ◽  
Chemotherapy Response ◽  
Long Term Outcomes ◽  
Luminal A ◽  
Molecular Subtyping ◽  
Luminal B ◽  
Luminal Type ◽  
Basal Type

10597 Background: Classification of breast cancers into molecular subtypes may be important for the proper selection of therapy for patients with early breast cancer. Previous analyses had shown that breast cancer subtypes have distinct clinical outcome (Sorlie, PNAS, 2001; Esserman, BCRT, 2011). Herein, we analyze using MammaPrint together with an 80-gene molecular subtyping profile (BluePrint) the response to neo-adjuvant chemotherapy and long term outcomes. Methods: This study was carried out on data from 144 patients from the I-SPY I trial; 232 patients from biomarker discovery program at MD Anderson (133 and 99 respectively; Hess, 2006, JCO; Iwamoto, 2011, BCRT); and 68 patients from City of Hope (Somlo, ASCO, 2010). All patients were treated in the neo-adjuvant setting with standard chemotherapy. MammaPrint and BluePrint were determined on 44K Agilent arrays run at Agendia or available through the I-SPY 1 data portal, or from Affymetrix U133A arrays. MammaPrint and BluePrint resulted in 4 distinct molecular groups: Luminal A (MammaPrint Low-risk/Luminal-type), Luminal B (MammaPrint High-risk/Luminal-type), Basal-type and HER2-type. Results: The overall pCR of this patient cohort was 22% but differed substantially among the subgroups. pCR was observed in 5% of the Luminal-A samples and 10% of Luminal-B, in 39% of the HER2-type samples and in 33% of the Basal-type samples. Patients with Basal-type tumors had a 5-year DFS of 71%; HER2-type had a 5-year DFS of 67%(n=71); 69% in HER2-type subgroup not treated with HER2-targeted therapy (n=45); Luminal-B type had a 5-year DFS of 77% and Luminal-A type showed 5-year DFS of 95%. Conclusions: We observed marked differences in response and DFS to neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint. These findings confirm differences in chemotherapy response among molecular subgroups and indicate that the BluePrint and MP profile used for this analysis helps to further establish a clinical correlation between molecular subtyping and treatment outcomes.

scholarly journals Whole‐Transcriptome Analysis ofPlasmodium falciparumField Isolates: Identification of New Pathogenicity Factors

2007 ◽  
Vol 196 (11) ◽  
pp. 1603-1612 ◽  
Author(s):  
Anthony Siau ◽  
Fousseyni S. Touré ◽  
Odile Ouwe‐Missi‐Oukem‐Boyer ◽  
Liliane Cicéron ◽  
Nassira Mahmoudi ◽  
...  
Keyword(s):  
Transcriptome Analysis ◽  
Pathogenicity Factors ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome

Prognostic Signicance of Cellular Iron Metabolism in Breast Cancer

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Rizwan Ullah Khan ◽  
Amber Hassan ◽  
Imrana Tanvir ◽  
Kashifa Ehsan
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Ki 67 ◽  
Luminal B ◽  
Cellular Iron ◽  
Menopausal Women ◽  
New Strategy ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Post Menopausal

Breast carcinoma is among the most common malignancy in women. Abstract:Original ArticleAim of the present study was to evaluate the prognostic signicance of iron expression in the biopsies of patients with breast cancer Objective:24 breast biopsies were studied. 19 cases were poorly differentiated, 5 cases were moderately differentiated and there was no well differentiated case. Iron, Estrogen receptor (ER), Progesterone receptor (PR), HER2 and Ki-67 immunohistochemical staining was performed for all these cases. Methods: Among the 5 moderately differentiated cases, 3 (60%) were positive for iron staining and among 19 poorly differentiated cases, 11 cases (57.89%) were positive. More iron positive cases (7 out of 14) were triple positive belonging to Luminal B class. Out of 14 iron positive cases, 11 were positive for HER2, 10 for ER, 9 for PR and all positive for Ki-67. Results: Iron deciency in premenopausal and overload in post-menopausal women can contribute to the development of breast carcinoma. So, iron can be considered as a cheap and effective marker for the prognosis of breast cancer. Association between a rise in iron levels and HER2 expression may provide new strategy for breast cancer treatment.

Molecular profiles of genomically high risk ER+ HER2- breast cancer tumors classified as functionally basal or luminal B by the 80-gene signature.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 563-563
Author(s):  
Joyce O'Shaughnessy ◽  
Virginia G. Kaklamani ◽  
Yuan Yuan ◽  
Julie Barone ◽  
Sami Diab ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Breast Cancers ◽  
Luminal B ◽  
Estrogen Response ◽  
Luminal Type ◽  
Basal Type

563 Background: The 80-gene signature (BluePrint/BP) classifies early-stage breast cancers based on functional molecular pathways as luminal, HER2, or Basal-type. In the NBRST study, 13% of immunochemistry (IHC) defined ER+ HER2- cancers reclassified as Basal-type by the BP assay (ER+ Basal), and these had worse prognosis but responded better to neoadjuvant chemotherapy than ER+ HER2- cancers classified as genomically luminal-type. The 70-gene risk of recurrence signature (MammaPrint/MP) further stratifies luminal-type cancers into low risk luminal A or high risk (HR) luminal B. HR cancers can be further stratified into High 1 (H1) or High 2 (H2), and the I-SPY2 trial has shown higher pCR rates in ER+ cancers classified as H2. Here, we investigated biological differences among ER+ Basal, ER- Basal, H1 luminal B, and H2 luminal B cancers by full transcriptome analysis. Methods: From the FLEX Study (NCT03053193), 1501 breast cancers with known IHC ER status were classified by MP and BP: 103 ER+ Basal, 210 ER- Basal and 1188 luminal B (H1 n=1034, H2 n=154). Clinical factors were assessed by either the Chi-square or Fisher’s exact tests; ANOVA or t test were used to analyze age. Differentially expressed genes (DEGs) were detected using Limma and pathway analyses were performed with GSEA. DEGs with a fold change >2 and FDR < 0.05 were considered significant. Results: Basal-type cancers (ER+/ER-) were larger and higher grade than luminal B cancers. Clustering analysis showed similar transcriptional profiles between ER+ Basal and ER- Basal cancers, distinct from luminal B cancers. Few DEGs were detected between ER+ Basal and ER- Basal cancers, and significantly more DEGs were found between ER+ Basal and luminal B cancers. Only three upregulated genes were detected in ER+ Basal compared to ER- Basal cancers: ESR1 and two immune-related genes ( FDCSP and LTF). Enrichment analysis of DEGs indicated increased immune activation and cell proliferation in ER+ Basal and ER- Basal cancers, and decreased estrogen response between ER+ Basal and luminal B cancers. Enrichment analysis between luminal B H1 and H2 cancers showed H2 cancers had higher immune activation and cell proliferation and lower estrogen response. Conclusions: Reclassification by BP of IHC defined ER+ HER2- cancers identified a subgroup of ER+ cancers that are biologically closer to ER- Basal than luminal-type cancers. Significant differences in response to neoadjuvant chemotherapy that have been seen between ER+ Basal and luminal B breast cancers lend support to the clinical importance of these findings. These data explain the poor prognosis observed in patients with ER+ Basal cancers and suggest that optimized chemotherapy, such as that for triple negative cancer, might be of benefit. BP provides clinically actionable information beyond pathological subtyping, which may guide neoadjuvant treatment recommendations. Clinical trial information: NCT03053193.

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