The NSABP B-14 and the NSABP B-20 Trial were used for the development and validation of the 21-gene reverse transcription polymerase chain reaction (RT-PCR) recurrence score assay to predict recurrence of estrogen receptor (ER)-positive, node-negative breast cancer.

  • A multistep approach was used for the synthesis and development of the:
    • Oncotype DX 21-gene RT-PCR assay
  • The developers selected:
    • 250 candidate genes from:
      • Published literature
      • Genomic databases, and
      • Experiments based on:
        • DNA array:
          • Performed on fresh frozen tissue
  • Data were then analyzed from:
    • Three independent studies:
      • Of breast cancer patients:
        • Involving a total of 447 patients:
          • Including the tamoxifen-only group of:
            • The NSABP B-20
    • This data was used to test the relationship between:
      • Expression of the 250 genes:
        • And the recurrence of breast cancer
    • These data was used to select:
      • The final 21-gene panel and
      • To develop an algorithm:
        • To determine the recurrence score (RS):
          • For each tumor sample
  • Finally:
    • This assay was validated by:
      • Calculating RS on cancer cells contained in paraffin blocks:
        • From patients in the NSABP B-14 trial
    • In multivariable Cox model:
      • The RS provided significant predictive power:
        • For recurrence:
          • That was independent of:
            • Age and
            • Tumor size
      • The RS was also:
        • Predictive of:
          • Overall survival (OS) and
            • Could be used as a continuous function to:
              • Predict distant recurrence in individual patients
  • The NSABP B-14 trial:
    • Was designed to assess the effect of tamoxifen on disease-free survival and OS:
      • In patients with breast cancer that are:
        • ER-positive
        • Lymph node-negative
  • The NSABP B-20 trial:
    • Evaluated the benefit of two chemotherapy regimens:
      • Methotrexate and fluorouracil followed by leucovorin vs
      • Cyclophosphamide, methotrexate, and fluorouracil) and
      • Tamoxifen over tamoxifen alone:
        • In patients with:
          • ER-positive
          • Lymph node-negative breast cancer
  • Further evaluation by the Oncotype DX, 21-gene RT-PCR assay:
    • Of 651 tissue blocks from the NSABP B-20 trial:
      • Showed additional clinical value of this score:
        • For weighing the benefit of chemotherapy for different ER-positive, lymph-node-negative breast cancer patients:
          • Treated with surgery and tamoxifen
      • Patients with a high RS (≥31):
        • Had significant benefit from chemotherapy:
          • With a decrease in 10-year distant recurrence rate
      • While patients with a low RS (<18):
        • Had minimal benefit from chemotherapy
      • The results of patients with intermediate RS scores (18 to 30):
        • Were uncertain
      • The clinical utility of this assay to stratify patients into low- (RS less than 18) , intermediate- (RS 18 to 30), and high-risk (RS ≥31) groups:
        • Can be applied not only to the prediction of recurrence:
          • But also to decision making with regard to chemotherapy:
            • In patients with ER-positive, lymph-node-negative breast cancer treated with tamoxifen
  • The additional analysis of 895 samples:
    • From patients treated with tamoxifen in both the B-14 and B-20 trials:
      • 355 patients given placebo from B-14 and
      • 424 patients treated with chemotherapy and tamoxifen from B-20:
        • Has provided further evidence for the clinical use of the the Oncotype DX assay recurrence score
    • In addition to predicting chemotherapy benefit and distant recurrence:
      • These data have also shown significant correlation with:
        • Locoregional recurrence:
          • Based on RS
      • In the patients given tamoxifen:
        • 10-year estimates of locoregional recurrence were:
          • 4.3% for patients with a low RS (<18) and
          • 15.8% for patients with a high RS (>30)
            • This trend was also evident in the patients who received placebo or chemotherapy and tamoxifen
  • The NSABP B-17 trial:
    • Compared lumpectomy alone with lumpectomy plus breast radiation in:
      • 818 patients:
        • Who had localized ductal carcinoma in situ (DCIS)
  • The NSABP B-18 trial:
    • Evaluated if preoperative versus postoperative chemotherapy with:
      • Adriamycin and cyclophosphamide:
        • Was more effective in prolonging:
          • Disease-free survival and OS in patients with operable breast cancer
  • The NSABP B-24 trial:
    • Examined the benefit of tamoxifen after lumpectomy and radiotherapy in patients with DCIS in:
      • Decreasing the occurrence of cancer in both breasts
  • The NSABP B-27 trial:
    • Compared three chemotherapy regimens:
      • Preoperative adriamycin and cyclophosphamide alone versus
      • The addition of taxotere preoperatively or postoperatively and
        • The effect on survival
  • The NSABP B-35 trial:
    • Compared the use of tamoxifen versus anastrozole after lumpectomy and radiotherapy to treat ER- and progesterone-positive DCIS in both pre- and postmenopausal women:
      • With regard to prevention of breast cancer occurrences


  1. Mamounas EP, Tang G, Fisher B, et al. Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Onc. 2010;28:1677-1683.
  2. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. New Engl J Med. 2004;351:2817-2826.
  3. 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;24:3726-3734.

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