Breast

• Gene expression profiles are associated with overall survival for several tumor types, including breast (N Engl J Med 2007;356:217)
• Several multigene prognostic products are commercially successful, including Oncotype DX^® and MammaPrint^® (Oncologist 2008;13:477, Adv Anat Pathol 2009;16:204)
• US Food and Drug Administration (FDA) has in vitro diagnostic multivariate index assay (IVDMIA) classification for these tests (US FDA: In Vitro Diagnostic Multivariate Index Assays [Accessed 10 September 2018])
• For all tests, the relationship of predicted to observed risk in different populations and their incremental contribution over conventional predictors, optimal implementation and relevance to patients receiving current therapies need further study (Ann Intern Med 2008;148:358, Ann Oncol 2007;18 Suppl 6:vi58, Genet Med 2009;11:66)
• Testing most valuable for ER+ HER2- patients (Breast 2011;20:S87)

• 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

• 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)

• 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

• 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

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

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.

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Reference: Multigene products