Oncotype DX 21 Gene Recurrence Score is Better in Predicting Cancer Recurrence Than Traditional Clinical Parameters

• ER positive tumors:
  • Can be very sensitive to endocrine therapy:
    • Which may allow some patients to safely avoid chemotherapy
• However:
  • The presence of ER receptors on immunohistochemistry:
    • Does not necessarily mean that the tumor’s growth:
      • Is being driven by ER-related pathways
  • Additionally, other molecular features may influence the tumor cells’ sensitivity to hormonal therapy
• The development of predictive molecular assays has been a major advancement in the field:
  • The assay measures mRNA expression of 21 genes:
    • Using reverse transcriptase-polymerase chain reaction techniques
  • It can be performed on formalin-fixed paraffin-embedded tumor specimens:
    • Obtained by core biopsy or surgery
  • It has been validated in ER+, node-negative women:
    • Who have not received any prior therapy
  • This assay is more reliable in predicting cancer recurrence than such clinical parameters as:
    • Size
    • Hormone receptor status
    • Nuclear grade
    • Ki-67
  • The assay measures:
    • Downstream ER-regulated genes:
      • To assess the functionality of the ER receptor
  • Patients with low scores (< 18) are considered at low risk for disease recurrence:
    • May not receive any benefit from adjuvant chemotherapy:
      • These patients are now treated with hormonal therapy alone without cytotoxic chemotherapy
    • In fact, the recently published subset analysis of the prospective validation of the 21-gene expression assay in breast cancer:
      • Confirmed that 98.7% of women:
        • With 21-gene signature scores of less than 10:
          • Managed with endocrine therapy alone had no evidence of local, regional, or distant recurrence at 5 years
        • Patients with a high score (> 31):
        • Have been shown to gain a large benefit from the addition of chemotherapy
          
      • While the assay is not performed on HER2-overexpressing tumors:
        • It does measure HER2 and other proliferative genes
  • It is currently only validated for:
    • Node-negative patients:
      • Although the RxPONDER (SWOG 1007) trial:
        • Is currently evaluating women with:
          • 1 to 3 positive lymph nodes and an 21-gene signature score of less than 25
        • These patients were randomized to receive chemotherapy and endocrine therapy to endocrine therapy alone:
          • We are awaiting the results of this trial
• References
• Paik S. Development and clinical utility of a 21-gene recurrence score prognostic assay in patients with early breast cancer treated with tamoxifen. Oncologist. 2007;12(6):631-635.
• Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351(27):2817-2826.
• Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24(23):3726-3734.
• Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. New Engl J Med. 2015;373(21):2005-2014.

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