Clinical question: Can a 21-gene recurrence score identify women with HR-positive, HER2-negative, node-negative breast cancer who can omit adjuvant chemotherapy?
Design: Prospective phase III randomized trial. 10,253 eligible women; the randomized intermediate-score population included 6,711 women with recurrence score 11–25. Endocrine therapy (ET) versus chemoendocrine therapy (CET). Median follow-up 90 months.
Invasive DFS: 83.3% ET vs 84.3% CET; absolute difference 1.0 point; HR 1.08 (95% CI 0.94–1.24; P=.26). Non-inferiority was demonstrated.
Distant recurrence-free: 94.5% vs 95.0%, difference 0.5 points; HR 1.03, P=.80.
Local/regional or distant recurrence-free: 92.2% vs 92.9%, difference 0.7 points; HR 1.12, P=.28.
OS: 93.9% vs 93.8%, difference −0.1 points; HR 0.97, P=.80.
No NNT is assigned. The trial is a non-inferiority strategy trial and the observed differences do not establish a chemotherapy benefit in the overall RS 11–25 population. A numerical NNT from a 1-point difference would be misleading.
Chemotherapy benefit varied by age and recurrence score. Women ≤50 with RS 16–25 had evidence of some chemotherapy benefit, an interaction that is clinically important and prevents interpreting TAILORx as “no chemotherapy for every intermediate score.”
The randomized comparison tested ET versus CET within RS 11–25 after the trial assigned patients with RS ≤10 to ET alone and RS ≥26 to chemotherapy plus ET. The primary endpoint was invasive DFS, with prespecified non-inferiority methodology.
TAILORx converted a genomic risk score into a treatment-selection tool. For most women in the randomized intermediate-score group, adding chemotherapy produced essentially no clinically meaningful improvement in 9-year invasive DFS, distant recurrence-free survival or OS. The value of the test is therefore not that it predicts prognosis alone; it identifies a large group in whom chemotherapy can be omitted while preserving outcomes, with age-specific nuance around RS 16–25 in younger women.
TAILORx supports omitting adjuvant chemotherapy for most women with node-negative HR-positive/HER2-negative breast cancer and a midrange 21-gene recurrence score, with age/menopausal status and score range affecting interpretation. It does not apply to node-positive disease or other tumour subtypes; integrate genomic testing with clinicopathological risk and current adjuvant endocrine/targeted options.