A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer

N Engl J Med. 2004 Dec 30;351(27):2817-26. doi: 10.1056/NEJMoa041588. Epub 2004 Dec 10.

Abstract

Background: The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures.

Methods: We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient.

Results: Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients.

Conclusions: The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / metabolism*
  • Estrogen Antagonists / therapeutic use
  • Female
  • Follow-Up Studies
  • Gene Expression*
  • Genes, erbB-2
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Recurrence
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk
  • Survival Analysis
  • Tamoxifen / therapeutic use*

Substances

  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Estrogen Antagonists
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen