Overview

The PAM50 intrinsic subtypes help you provide an individualized risk assessment1
 

Enhance your treatment decisions with intrinsic subtypes

 

Put your patients’ prognostic information into action

  • Prosigna was developed based on the PAM50 gene signature, which measures the expression of 50 genes to classify tumors into 1 of 4 intrinsic subtypes1
  • Intrinsic subtypes provide valuable prognostic information to guide clinical decisions1,2
  • According to the St. Gallen guidelines, systemic therapy recommendations should follow intrinsic subtype classification2

chart_intrinsic_subtypes.jpg

Intrinsic subtypes: the underlying biology of breast cancer

PAM50 is the accepted standard for subtyping breast cancer3

The Cancer Genome Atlas (TCGA) research network analyzed the gene expression signatures of 525 breast cancer tumors and clustered them into 4 intrinsic subtypes using 3 methods:

  • PAM50 gene signature
  • Unsupervised hierarchical clustering
  • Semi-supervised hierarchical clustering

PAM50 showed high concordance with both the unsupervised (P<0.001) and the semi-supervised (P<0.001) cluster analyses, supporting PAM50's role as a powerful tool for categorizing breast cancer by intrinsic subtype.

The research concluded that diverse genetic and epigenetic alterations converge phenotypically into the following 4 main breast cancer intrinsic subtypes defined by PAM50: luminal A, luminal B, HER2-enriched, and basal-like.

 

gene_expression_PAM50_heatMap_subtypes_NTV.png

 

References: 1. Prosigna [Package Insert]. Seattle, WA: NanoString Technologies, Inc; 2013. 2. Goldhirsch A, Wood WC, Coates AS, et al. Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011;22(8):1736-1747. 3. The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61-70.

The PAM50 intrinsic subtypes help you provide an individualized risk assessment1

Use Prosigna to predict your patient’s Risk of Recurrence (ROR)*

Prosigna generates ROR from a proprietary algorithm1

  • Intrinsic subtypes are biologically and clinically distinct types of breast cancer that are characterized by different PAM50 gene expression signatures2,3
  • ROR is derived from a proprietary algorithm based on the PAM50 gene signature, intrinsic subtype, tumor size, nodal status, and proliferation score1
  • The gene expression profile of a patient’s tumor is compared to each of the defined intrinsic subtype gene signatures to determine the degree of similarity1
  • Proliferation score is determined by evaluating multiple genes within the proliferation pathway4
  • ROR is provided as a numerical score on a 0-to-100 scale that estimates the probability of distant recurrence over 10 years1

chart_risk_of_recurrence.jpg

 

*ROR score is Prosigna’s proprietary model for predicting risk of recurrence in a patient. Probability of recurrence cannot be guaranteed.



References: 1. Prosigna [Package Insert]. Seattle, WA: NanoString Technologies, Inc; 2013. 2. Parker JS, Mullins M, Cheang MC, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27(8):1160-1167. 3. Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747-752. 4. Bastien RRL, Ebbert MTW, Boucher KM, et al. Using the PAM50 breast cancer intrinsic classifier to assess risk in ER+ breast cancers: a direct comparison to Oncotype DX. Presented at: 47th American Society of Clinical Oncology Annual Meeting; June 3-7, 2011; Chicago, IL. Abstract 503. 5. Nielsen T, McDonald S, Kulkarni S, et al. Analytical reproducibility of the breast cancer intrinsic subtyping test and nCounter® Analysis System using formalin-fixed paraffin-embedded (FFPE) breast tumor specimens. Poster presented at: 102nd United States and Canadian Academy of Pathology Annual Meeting; March 2-8, 2013; Baltimore, MD. Abstract 2075. 6. Gnant M, Filipits M, Mlineritsch B, et al; Austrian Breast and Colorectal Cancer Study Group. Clinical validation of the PAM50 risk of recurrence (ROR) score for predicting residual risk of distant-recurrence (DR) after endocrine therapy in postmenopausal women with HR+ early breast cancer (EBC): an ABCSG study. Presented at: San Antonio Breast Cancer Symposium; December 4-8, 2012; San Antonio, TX. Abstract P2-10-02.

The PAM50 intrinsic subtypes help you provide an individualized risk assessment1

Accurately determine risk of recurrence with Prosigna

Risk of Recurrence (ROR) correlates with 10-year probability of distant recurrence1

The probability of distant recurrence within 10 years increases based on tumor size and nodal status. These data represent risk estimates derived from the clinical validation studies.1

Risk classification is also provided to allow interpretation of the ROR score by using cutoffs related to clinical outcome in tested patient populations.1 Three categorical risk groups (low, intermediate, and high) are defined based on predicted risk of distant recurrence at 10 years.2

breast_cancer_recurrence_chart_10year_drfs.jpg

References: 1. Prosigna [Package Insert]. Seattle, WA: NanoString Technologies, Inc; 2013. 2. Dowsett M, Sestak I, Lopez-Knowles E, et al. Comparison of PAM50 risk of recurrence score with Oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy. J Clin Oncol. 2013;31(22):2783-2790.

Prosigna is indicated for use in postmenopausal women with hormone receptor-positive, node-negative (Stage I or II) or node-positive (Stage II or IIIA) early-stage breast cancer to be treated with adjuvant endocrine therapy.

 

© 2014-2017 NanoString Technologies, Inc. All rights reserved. NanoString, the NanoString Technologies logo, nCounter, Prosigna and the Prosigna logo are trademarks and/or registered trademarks of NanoString Technologies, Inc. in various jurisdictions.