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.