The human nCounter Breast Cancer 360 panel and data analysis service provides a unique 360 degree view of gene expression for the breast tumor microenvironment and immune response. Now researchers can more quickly decode the complexities of breast cancer biology, develop novel breast cancer gene signatures, and categorize disease heterogeneity using 48 biological signatures including signatures based upon the validated PAM50 and Tumor Inflammation Signature* (TIS) assays.
- Expertly curated, comprehensive content includes 776 genes across 23 key breast cancer pathways and processes
- Provides a unique 360 degree view of gene expression for the breast tumor microenvironment and immune response
- Interactive Breast Cancer 360 data analysis report available to expedite analysis to insight
- 48 signatures across 13 categories measuring biological variables crucial to breast cancer tumor biology
- Access to validated signatures: PAM50, Tumor Inflammation Signature (TIS), Risk of Recurrence (ROR)/Genomic Risk
- Expanded evaluation of breast cancer subtypes including: PAM50 Signature, TNBC, and Claudin-Low Signature
- Publication ready figures and statistical methods included for speed to presentation
*Ayers, Mark, et al. "IFN-y-related mRNA profile predicts clinical response to PD-1 blockade." The Journal of Clinical Investigation 127.8 (2017).
|Signatures Based Upon Validated PAM50 and TIS Signatures|
|Risk of Recurrence||The Risk of Recurrence score (ROR) is an integer value on a 0–100 scale that is related to an individual patient’s probability of distant recurrence within 10 years of diagnosis, with 0 being lowest risk and 100 being highest risk. The ROR score is calculated by comparing the expression profiles of 46 genes in the sample with the four PAM50 centroids, to calculate four different correlation values. These correlation values are then combined with the PAM50 proliferation score and the tumor size to calculate the ROR score. When nodal status is provided, these scores can be classified into low, intermediate, and high-risk categories.|
|Genomic Risk||The Genomic Risk of Recurrence score (Genomic Risk) is calculated by comparing the expression profiles of 46 genes in the sample with the four PAM50 centroids, to calculate four different correlation values. These correlation values are then combined with the PAM50 proliferation score to estimate the genomic risk of distant recurrence. The results are reported on a scale of 0 to 100, with 0 being lowest risk and 100 being highest risk. This score is distinct from the Risk of Recurrence (ROR) score, as it does not include the tumor size included in the score calculation – it is solely based on the genomic data.|
|PAM50 Molecular Subtypes||This 50-gene signature measures a gene expression profile that allows for the classification of breast cancer into four biologically distinct subtypes (Luminal A, Luminal B, HER2-Enriched, Basal-like).|
|Luminal A Correlation Value||Luminal A tumors are typically characterized by high expression of estrogen receptor (ER), progesterone receptor (PR), and genes associated with ER activation1. These tumors are low-grade, tend to grow slowly, exhibit low expression of genes associated with cell cycle activation and have the best prognosis.|
|Luminal B Correlation Value||Luminal B tumors are typically characterized by high expression of estrogen receptor (ER), progesterone receptor (PR), and genes associated with ER activation1. These tumors tend to grow slightly faster than Luminal A tumors, exhibit high expression of genes associated with cell cycle activation and proliferation, and have a slightly worse prognosis than Luminal A tumors.|
|HER2-Enriched Correlation Value||HER2-Enriched tumors are typically characterized as clinically HER2 positive breast cancer as defined by traditional IHC/FISH criteria. Some studies have indicated that the HER2-Enriched molecular subtype may be a better predictor of response to HER2-targeted therapies when compared with IHC and FISH.|
|Basal-like Correlation Value||Basal-like tumors are typically characterized as having low expression of ER, PR, and HER2. Most clinically triple negative tumors are Basal-like subtype by molecular profiling. These tumors are poorly differentiated invasive high-grade ductal carcinomas that by have metastatic properties.|
|Proliferation (PAM50)||This signature outputs the PAM50 proliferation score by measuring key genes involved in breast tumor proliferation. In some cases, a highly proliferative breast tumor may correlate with an increase in disease progression or metastasis.|
|Tumor Inflammation Signature (TIS)||Tumor Inflammation Signature. TIS measures the abundance of a peripherally suppressed adaptive immune response within the tumor.
|Claudin-Low Signature||This molecular subtype is characterized by low levels of luminal differentiation markers, high enrichment for epithelial-to-mesenchymal transition markers, immune response and cancer stem cell-like genes.|
|TNBC Signature||This signature identifies four distinct TNBC subtypes: Luminal/AR subtype 1, characterized by AR, ER, prolactin and ErbB4 signaling; Mesenchymal subtype 2, characterized by cell cycle, mismatch repair, and DNA damage networks; Basal-like Immune-Suppressed subtype 3, characterized by downregulation of B, T and NK-cells immune-regulating and cytokine pathways; Basal-like Immune Activated subtype 4, characterized by upregulation of B, T and NK cells immune-regulating pathways, and activation of STAT.|
|CDK4 Expression||Cyclin-dependent kinases 4 and 6 (CDK4/6) play a key role in the regulation of proliferation in normal breast tissue and breast tumors. CDK4/6 inhibitors have been indicated in hormone receptor (HR) positive metastatic breast cancer. Cyclin-dependent kinase 4 (CDK4) is an enzyme encoded by the CDK4 gene, mutations in this gene as well as in its related proteins have been shown to be associated with tumorigenesis.|
|CDK6 Expression||Cyclin-dependent kinases 4 and 6 (CDK4/6) play a key role in the regulation of proliferation in normal breast tissue and breast tumors. CDK4/6 inhibitors have been indicated in hormone receptor (HR) positive metastatic breast cancer. CDK6, as well as CDK4, has been shown to phosphorylate and regulate the activity of the tumor suppressor protein Retinoblastoma and indicating a role in cancer development.|
|Differentiation||This signature assigns a score of differentiation to the sample. Well-differentiated tumors that is phenotypically more similar to normal cells or tissue will grow and spread at a slow rated compared with poorly differentiated tumors, these present with abnormal cells that often grow rapidly.|
|Breast Cancer p53 Signature||This signature categorizes p53 status by mutant-like vs wild-type-like in breast cancer and the signature is significantly associated with overall survival in breast cancer, identifying a group with high unmet need.|
|BRCAness Signature||This signature captures breast cancer biology that is informative as to defects in the DNA damage repair-genes BRCA1 and BRCA2. Similar to the Homologous Recombination Deficiency signature this captures breakdown in DNA damage repair, however, these are specific to BRCA-related mutations and more heavily weighted to BRCA1 mutants.|
|HRD Signature||This signature is used to functionally assess Homologous Recombination Repair status, with potential to predict sensitivity to DNA-damage repair inhibitors such as PARP inhibitors. This captures cell cycle regulation, DNA damage, DNA replication, and DNA recombination and repair pathways. Additionally, this signature is also used to predict overall survival in breast cancer.|
|ER Signaling Signature||Estrogen-binding systems associate with various proteins that direct cell cycle signaling, proliferation and survival. This signature captures ER-mediated signaling pathways to elucidate how ER modulates activity of key transcription factors through stabilizing DNA-protein complexes and recruiting co-activators. This signature also captures the impact to other signaling pathways induced by the binding of estrogens in the nuclear causing conformational changes in the receptors.|
|PTEN/AKT||Phosphatase and tensin homolog gene expression. PTEN is a tumor suppressor gene that functions through the regulation of the Akt/PKB signaling pathway. Mutations or loss of PTEN expression are common across a range of cancer types, including breast cancer.|
|Tumor/Immune Activity Signatures|
|FOXA1||Cell Adhesion||Mammary Stemness||Rb1||SOX2|
|Cytotoxic Cells||CD8 T-Cells||Macrophages||Mast Cells||Treg|
Includes expertly curated 776 genes across 23 categories of breast cancer tumor biology to support the evaluation of pathways and process, as well as novel signature development.
|Cell Cycle||ER Signaling||Chromatin Modification||Hedgehog||MAPK||Wnt|
|Breast Cancer Subtypes||Cancer Progression EMT||Immune Cell Marker|
|Triple Negative Tumor Biology||Microenvironment Tissue Marker||Immune Infiltration|
|Tumor Metabolism||Cancer Progression||Immune Response|
Content included in the Breast Cancer 360 panel allows for a more comprehensive measurement of biological variables crucial to tumor progression and response to a wide-range of treatments. Research signatures are enriched with potentially predictive genes involved in proliferation, endothelial, angiogenesis, cytotoxicity, stroma, inflammatory chemokines, and apoptosis.
- 48 signatures including two analytically validated signatures- PAM501,2 and Tumor Inflammation Signature3
- 10 research focused signatures and 30 novel signatures measuring important tumor and immune activities
- adapted to decode breast cancer biology in concert
Analytically Validated Signatures
Included with the Breast Cancer 360 panel is the PAM50 Signature. This 50-gene signature measures a gene expression profile that allows for the classification of breast cancer into four biologically distinct subtypes and a prognostic score.
- PAM50 Subtype
- Luminal A
- Luminal B
- Prosigna Score / Risk of Recurrence
Tumor Inflammation Signature3
Included with the Breast Cancer 360 panel is the Tumor Inflammation Signature. This 18-gene signature measures activity known to be associated with response to PD-1/PD-L1 inhibitors pathway blockade3.
- Includes 4 Areas of immune biology used to determine peripherally suppressed immune response and the identification of “hot” or “cold” tumors
- Antigen Presenting Cells
- T Cell/NK presence
- IFNγ Biology
- T Cell Exhaustion
- Tissue-of-origin agnostic (Pan-cancer)
- Potential surrogate for PD-L1 and mutational load in research setting4
|18-gene Tumor Inflammation Signature|
|Number of Targets||776 (Human), Including internal reference genes|
|Sample Input – Standard (No amplification required)||50 – 300 ng|
|Sample Input – Low Input||As little as 10 ng with nCounter RNA Low Input Kit and Panel specific primer pools (sold separately)|
|Breast Cancer 360 Panel Standard||Synthetic oligonucleotide pool corresponding to all panel gene targets used for normalization|
|Sample Type(s)||FFPE-derived RNA, total RNA, and cell lysates|
|Customizable||Add up to 30 unique genes with Panel-Plus|
|Time to Results||Approximately 24 hours|
|Data Analysis||nSolver Analysis software, BC 360 Data Analysis Service|
- Asleh K et al. Predictive Biomarkers for Adjuvant Capecitabine Benefit in Early-Stage Triple-Negative Breast Cancer in the FinXX Clinical Trial. Clinical Cancer Research. January 31, 2020.
- Waks AG et al. The Immune Microenvironment in Hormone Receptor-Positive Breast Cancer Before and After Preoperative Chemotherapy. Clinical Cancer Research. 2019;25(15)4644:4655.
- Pascual T et al. Significant Clinical Activity of Olaparib in a Somatic BRCA1-Mutated Triple-Negative Breast Cancer With Brain Metastasis. JCO Precision Oncology. 2019;3:1-6.
- Adamo B et al. Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial. Breast Cancer Research. 2019;21(1):108.
- Lee J et al. Phase I clinical trial of the combination of eribulin and everolimus in patients with metastatic triple-negative breast cancer. Breast Cancer Research. 2019;21(1): 119.
For Research Use Only. Not for use in diagnostic procedures.