TABLE A-1 Archival Tissue Used in the Development of Oncotype DX Computational Model and Gene List

Study Paik et al., 2003 Cobleigh et al., 2005 Esteban et al., 2003
Tissue source Tamoxifen arm of NSABP B-20 Rush Presbyterian-St. Luke’s Hospital Providence St. Joseph’s Hospital
Sample # 233 78 136
Lymph-node status Negative > 10 positive nodes Positive or negative
Estrogen-receptor status Positive Positive and negative Positive and negative
Treatment Tamoxifen (100%) Tamoxifen (54%) Chemotherapy (80%) Tamoxifen (41%) Chemotherapy (39%)
NOTE: NSABP = National Surgical Adjuvant Breast and Bowel Project.
SOURCE: Shak (2011).

Analytical Validation

The analytical validity of Oncotype DX was assessed in the Agency for Healthcare Research and Quality (AHRQ) report, Impact of Gene Expression Profiling Tests on Breast Cancer Outcomes (AHRQ, 2008). The report noted there is evidence about Oncotype DX’s assay performance and laboratory characteristics as well as some limited information on its reproducibility. Cronin et al. (2007) found that Oncotype DX met acceptable operational performance ranges with minimal assay imprecision due to instrument, operator, reagent, and day-to-day baseline variation. Investigators also conducted technical feasibility studies during assay development, including analysis of preanalytical factors such as variability in preparation, tumor block age, and dissection (Shak, 2011). Paik and colleagues (2004) measured and reported the reproducibility within and between blocks in the clinical validation study.

Statistical and Bioinformatics Validation

The computational procedures used to determine the Recurrence Score are published, and there is public information that provides an overview of how the computational model was generated (see Discovery Phase) (Paik et al., 2004). The supplementary materials of Paik et al. (2004) note that the investigators weighted the NSABP B-20 results most heavily in selecting the final gene list and developing the computational model because investigators planned to clinically validate the test in similar archival tissue from NSABP B-14 patients. However, more detailed information on model

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