21-Gene Recurrence Score Assay As a Predictor of Adjuvant Chemotherapy Administration for Early-Stage Breast Cancer: An Analysis of Use, Therapeutic Implications, and Disparity Profile

J Clin Oncol. 2016 Jun 10;34(17):1995-2002. doi: 10.1200/JCO.2015.65.0887. Epub 2016 Mar 21.


Purpose: The 21-gene Recurrence Score (RS) assay is used to predict disease recurrence and benefit of chemotherapy in estrogen receptor-positive, lymph node-negative early-stage breast cancer (EBC). Our study is the first analysis of trends and differences in the use of the RS assay and its impact on recommending chemotherapy in a population-based data set.

Methods: Patients with EBC diagnosed from 2004 to 2012 and included in the National Cancer Data Base were analyzed. Multivariate logistic regression analysis was used to estimate the covariates associated with use of the test and its impact on chemotherapy decisions.

Results: The RS assay was ordered for 54.0% of the 143,032 identified patients. Of all the variables, RS assay had the strongest association with recommendation for chemotherapy, with an adjusted odds ratio (AOR) of 83 for high assay scores. When indicated, test use was significantly associated with younger age, white race, academic centers, private insurance, and pT2/pN0(i+) grade 2 to 3 disease. Black patients (AOR, 1.31; 95% CI, 1.20 to 1.43) and those treated in community facilities (AOR, 1.49; 95% CI, 1.35 to 1.63) were more likely to be tested outside the National Comprehensive Cancer Network guidelines. Black patients (AOR, 1.51; 95% CI, 1.31 to 1.69) and those with high tumor grade (AOR, 30.76; 95% CI, 26.48 to 35.73) had significantly higher assay scores. Younger black patients (AOR, 1.33; 95% CI, 1.16 to 1.54) were more likely to receive chemotherapy despite low assay scores.

Conclusion: The RS assay significantly influences clinicians' recommendations for chemotherapy in patients with EBC. Black patients tended to have higher assay scores, which may reflect use patterns or less favorable tumor biology for estrogen receptor-positive disease. There are significant differences in use and clinical implications of the test on the basis of race, insurance, and type of facility.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant
  • Female
  • Gene Expression Profiling / methods
  • Genetic Predisposition to Disease
  • Humans
  • Logistic Models
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Receptor, ErbB-2 / biosynthesis
  • Receptors, Estrogen / biosynthesis
  • Retrospective Studies


  • Receptors, Estrogen
  • ERBB2 protein, human
  • Receptor, ErbB-2