Breast cancer

Multigene products

Editor-in-Chief: Debra L. Zynger, M.D.
Emily S. Reisenbichler, M.D.

Last author update: 1 September 2018
Last staff update: 10 May 2021

Copyright: 2003-2023,, Inc.

PubMed Search: Breast multigene panels

Emily S. Reisenbichler, M.D.
Page views in 2022: 814
Page views in 2023 to date: 528
Cite this page: Reisenbichler ES. Multigene products. website. Accessed September 30th, 2023.
Definition / general
Essential features
  • New AJCC (8th edition) incorporates multigene panel results into staging, placing T1 and T2 hormone receptor positive, HER2- and lymph node negative tumors with low risk scores into the T1a-T1bN0M0 prognostic category
  • Multigene panels are not currently incorporated into staging for triple negative or HER2+ tumors
  • Use of these assays is not required for staging
  • Oncotype DX, with Level 1 evidence, is the only assay incorporated into the Pathological Prognostic Stage Table
  • No one multigene assay is preferred by the AJCC over another assay for treatment decisions
Oncotype Dx®
  • ER+, HER2 - tumors, can have up to 3 involved lymph nodes
  • Most widely accepted and used multigene expression assay; offered by Genomic Health
  • First available in January 2004
  • Measures changes in 21 genes on paraffin fixed tissue to predict likelihood of disease recurrence and which patients are most likely to respond to chemotherapy (Breast Cancer Res 2006;8:R25)
  • Results in recurrence score (RS) of 0 - 100, categorized into low (< 11), intermediate (11 - 25) or high (> 25) recurrence risk
  • TAILORx trial found that endocrine therapy was "noninferior" (comparable) to chemotherapy plus endocrine therapy for disease free survival in up to 85% of women with hormone receptor positive, early invasive breast cancer
  • Particularly relevant for women > 50 years old with a recurrence score ≤ 25 as they may be spared adjuvant chemotherapy (N Engl J Med 2018;379:111)
Breast Cancer Index
  • 11 gene assay including 4 normalization genes; offered by BioTheranostics
  • Results are predictive for benefit of extended endocrine therapy and prognostic for the risk of late (> 5 years) and overall (0 - 10 years) distant recurrence following 5 years of endocrine therapy
  • ER+ tumors can have up to 3 involved lymph nodes
  • Breast Cancer Index prognostic score reported as continuous percentage risk of late distant recurrence (> 5 years) and Breast Cancer Index predictive score reported as categorical (low versus high) likelihood of benefit from extended endocrine therapy
  • Breast Cancer Index scores resulted in a 26% net decrease in the recommendation of extended endocrine therapy (Breast Cancer Res Treat 2015;154:533)
  • 12 gene expression assay, including 3 proliferation related genes, 5 hormone related, 3 normalization genes and 1 control gene for DNA contamination (Br J Cancer 2015;112:1405)
  • ER+, HER2- tumors, can have up to 3 involved lymph nodes
  • EPclin Risk Score integrates the 12 gene molecular score with tumor size and nodal status to categorize patients into low or high risk of distant recurrence within 10 years if treated with 5 years of endocrine therapy alone
  • 70 gene assay, originally developed in 2002 to determine risk of distant metastases (Nature 2002;415:530); offered by Agendia
  • Originally FDA approved in 2007, requiring fresh tissue but later FDA approved in 2015 for formalin fixed paraffin embedded tissue
  • No estrogen or HER2 status restriction
  • Results in binary stratification into low risk or high risk of cancer recurrence within 10 years without any adjuvant treatment (either hormonal therapy or chemotherapy)
  • MINDACT trial found that 46% of women with early stage breast cancer at high clinical risk (defined as 10 year probability of breast cancer specific survival without systemic therapy of more than 88% for ER+ and more than 92% for ER- tumors as calculated by Adjuvant! Online version 8.0 [website currently under construction]) and low genomic risk for recurrence (as determined by MammaPrint low versus high risk result) may be spared adjuvant chemotherapy (N Engl J Med 2016;375:717)
PAM 50 (Prosigna)®
  • Developed by NanoString, the assay measures expression profiles of 50 genes by PCR and classifies them into intrinsic subtypes (luminal A, luminal B, HER2 enriched, basal-like)
  • Results in risk of recurrence score (ROR) of 0 - 100 that correlates with probability of distant recurrence within 10 years (BMC Med Genomics 2012;5:44, J Clin Oncol 2013;31:2783)
  • Can be used on stage 1 or stage 2 and lymph node negative for stage 2 with 1 to 3 positive nodes
  • Node negative cancers are classified as low (0 - 40), intermediate (41 - 60) or high (61 - 100) risk
  • Node positive cancers are classified as low (0 - 40) or high (41 - 100) risk
  • Is incorporated into the Prosigna Breast Cancer Prognostic Gene Signature Assay (BMC Med Genomics 2015;8:54)
  • Developed by Clarient Diagnostic Services
  • IHC evaluation of the expression of five genes (p53, NDRG1, CEACAM5, SLC7A5 and HTF9C) in early stage, hormone receptor positive breast cancers to predict outcomes (J Clin Oncol 2006;24:3039)
  • Subdivides patients into low, moderate and high risk, age specific groups
Prognostic factors
  • T1 and T2, hormone receptor-positive, HER2- and lymph node negative tumors with any of the following multigene panel results:
    • Oncotype Dx® recurrence score less than 11 (Level 1 Evidence)
    • Breast Cancer Index in the low risk range (Level 2 Evidence)
    • EndoPredict® low risk score (Level 2 Evidence)
    • Mammaprint® low risk score (Level 2 Evidence)
    • PAM 50® risk of recurrence score in the low range (Level 2 Evidence)
  • Are placed into the same prognostic category as T1a-T1bN0M0 tumors
Board review style question #1
    Which multigene test has been integrated into the 8th edition of AJCC staging system for breast cancer with Level 1 evidence?

  1. Oncotype Dx
  2. Breast Cancer Index
  3. Endopredict
  4. Mammaprint
  5. PAM 50
Board review style answer #1
A. The 21 - gene recurrence score from Oncotype Dx is incorporated into the 8th edition of AJCC staging for breast cancer based on Level 1 Evidence (large scale prospective clinical trial published data) indicating that for patients with ER positive, lymph node negative, tumors with a recurrence score < 11, prognosis is excellent.

Comment Here

Reference: Multigene products
Back to top
Image 01 Image 02