Prospective Validation of a 21-Gene Expression Assay in Breast Cancer

Abstract

BACKGROUND Prior studies with the use of a prospective–retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker. METHODS We performed a prospective trial involving women with hormone-receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative, axillary node–negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension (or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features. A reverse-transcriptase–polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue, and the results were used to calculate a score indicating the risk of breast-cancer recurrence; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10, indicating a very low risk of recurrence (on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence). RESULTS Of the 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease–free survival was 93.8% (95% confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3% (95% CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local–regional site was 98.7% (95% CI, 97.9 to 99.2), and the rate of overall survival was 98.0% (95% CI, 97.1 to 98.6). CONCLUSIONS Among patients with hormone-receptor–positive, HER2-negative, axillary node–negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features, those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.)

Uptake of a 21-Gene Expression Assay in Breast Cancer Practice: Views of Academic and Community-Based Oncologists

“…At the time of the interviews, the preliminary results of tailorx 29 were not available. Early results from that trial demonstrated that patients who had a very low recurrence score (0-10) and who received endocrine therapy alone (that is, no chemotherapy) experienced very low recurrence rates at 5 years 29 .…”

“…Early results from that trial demonstrated that patients who had a very low recurrence score (0-10) and who received endocrine therapy alone (that is, no chemotherapy) experienced very low recurrence rates at 5 years 29 . Had those results been available, participants might have had a different view of the evidence.…”

Second international consensus guidelines for breast cancer in young women (BCY2)

“…Prospective data from randomized trials (MINDACT, TailorX, X-PONDER, PLAN B) are awaited to assess the prognosis and benefit of chemotherapy according to age and tumor biology in the modern era. In the post-BCY2 preliminary report of the TailorX trial, young women were <5% of the total 50 . Thus, these tests should be used with caution in young women.…”

Clinical Utility of Multigene Profiling Assays in Early-Stage Breast Cancer

“…The ability of Oncotype dx to identify a very low-risk population (rate of freedom from distant recurrence at 5 years: 99.3%; 95% confidence interval: 98.7% to 99.6%) has been confirmed by an interim analysis from a prospective trial 25 . Although the Oncotype dx, Prosigna, and EndoPredict assays have all shown that, in the absence of chemotherapy treatment, patients stratified as low risk have a low risk of recurrence, prospective validation data are limited.…”

“…Accrual for tailorx is complete, but final results have not been published. A recent preliminary report provided data concerning survival and the rate of freedom from distant recurrence for the 1626 low-risk patients who received endocrine monotherapy 25 . Given that the preliminary report provided data only for the low-risk cohort, the reviewers did not believe that those data yet provide level IA evidence for the prognostic ability of Oncotype dx.…”