The 21-gene recurrence score assay (Oncotype DX)

  • The 21-gene recurrence score assay (Oncotype DX):
    • Is a reverse-transcriptase-polymerase-chain-reaction assay of:
      • 16 prospectively selected genes and 5 reference genes
    • Analysis is performed in:
      • Paraffin-embedded tumor tissue
    • This assay was developed from:
      • NSABP B-14 and validated with data and specimens from NSABP B-20
    • It estimates the 10-year risk of distant recurrence:
      • By categorizing results into:
        • Low-risk (RS< 18) group
        • Intermediate-risk (RS 18 to 30) group
        • High-risk (RS > 30) groups
    • A low recurrence score (RS < 18):
      • Predicts little benefit of chemotherapy
  • The 21-gene recurrence score assay:
    • Is proven to be prognostic for women with:
      • Node-negative
      • ER-positive breast cancer:
        • Treated with tamoxifen
  • Retrospective data obtained via optional tumor banking:
    • In accordance with the SWOG 8814 trial:
      • Which demonstrated postmenopausal women:
        • With node-positive, ER-positive tumors:
          • Achieved superior survival when:
            • Cyclophosphamide, doxorubicin, and fluorouracil:
              • Was given before tamoxifen
    • The SWOG 8814 trial:
      • Allowed for retrospective assessment of recurrence score on DFS by treatment group
      • Analysis demonstrated the recurrence score results:
        • To be both prognostic and predictive of benefit:
          • To adjuvant chemotherapy:
            • As there was no added benefit to adjuvant systemic chemotherapy:
              • In women with low recurrence scores and
              • There was an improvement of DFS:
                • In those with high recurrence scores
    • These hypothesis-generating results:
      • Serve as preliminary basis for the RxPonder trial:
        • Which is currently enrolling as a phase III trial
        • Randomizing women with hormone receptor-positive and HER2-negative breast cancer involving 1 to 3 lymph nodes and a 21-gene assay recurrence score of 25 or less to:
          • Endocrine therapy alone versus chemotherapy followed by endocrine therapy
    • The 21-gene recurrence score:
      • Is not used in patients with HER2-positive breast cancer
  • In women with hormone receptor positive (HR+), HER2-negative early breast cancer:
    • The 21-gene signature score provides prognostic information:
      • That is independent of clinical and pathological features
    • A high score (on a scale of 0 to 100):
      • Indicates a higher rate of distant recurrence
      • And is predictive of chemotherapy benefit
  • The prospective Trial Assigning Individualized Options for Treatment (TAILORx):
    • Showed that endocrine therapy alone was non-inferior to adjuvant chemotherapy plus endocrine (chemoendocrine) therapy:
      • In women with HR+, HER2-negative, axillary node-negative breast cancer and a 21-gene recurrence score of 11 to 25
      • An exploratory analysis indicated some benefit of chemotherapy in women 50 years of age or younger:
        • Who had a recurrence score of 16 to 25:
          • In this analysis there was a:
            • Small (~1.6%) chemotherapy benefit in distant disease-free survival for patients with recurrence score results from 16 to 20
            • Modest (~6.5%) chemotherapy benefit for patients with recurrence score results from 21 to 25
  • References:
    • 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.
    • Albain KS, Barlow WE, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11(1):55-65.
    • Ramsey SD, Barlow WE, Gonzalez-Angulo AM, et al. Integrating comparative effectiveness design elements and endpoints into a phase III, randomized clinical trial (SWOG S1007) evaluating oncotypeDX-guided management for women with breast cancer involving lymph nodes. Contemp Clin Trials. 2013;34(1):1-9.
    • Sparano JA, Gray RJ, Ravdin PM, Makower DF, Pritchard KI, Albain KS, et al. Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer. New Engl J Med. 2019;380(25):2395-2405.
    • Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. New Engl J Med. 2018;379(2):111-121.

#Arrangoiz #CancerSurgeon #BreastSurgeon #BreastCancer #SurgicalOncologist #OncotypeDx #CASO #CenterforAdvancedSurgicalOncology

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