title: The 21-Gene Recurrence Score Assay for Node-Positive, Early-Stage Breast Cancer and Impact of RxPONDER Trial on Chemotherapy Decision-Making: Have Clinicians Already Decided?
abstract: Background:The 21-gene recurrence score (RS) assay is retrospectively validated for assessing prognosis and benefit from chemotherapy in hormone receptor-positive, early-stage breast cancer (EBC) with low RS. We hypothesized that oncologists have already incorporated the RS assay for decision-making in higher-risk, node-positive disease, despite the lack of prospective data and contrary to NCCN Guideline recommendations. This study provides the first analysis of trends and differences in RS use and therapeutic implications in a population-based data set of patients with node-positive EBC. It also assesses the impact of the RxPONDER trial on clinicians' chemotherapy recommendations.Methods:Node-positive EBC cases diagnosed during 2010 through 2012 and included in the National Cancer Data Base were used. Multivariate logistic regression was used to estimate test use and impact on chemotherapy recommendations.Results:The RS assay was ordered for 16.5% of the 80,405 identified patients. Of all variables, the RS assay had the strongest association with chemotherapy recommendation, with adjusted odds ratios (AORs) of 19 for scores >30. Odds of chemotherapy recommendation were significantly lower for the group who received the test (AOR, 0.21; 95% CI, 0.20-0.22). When divided based on the cutoff point of 25 adopted by the RxPONDER trial, those with an RS of 18 to 25 had significantly lower odds of chemotherapy recommendation compared with those with an RS of 26 to 30 (AOR, 0.32; 95% CI, 0.26-0.40). Test use was lower for blacks, community centers, uninsured/governmentally insured patients, higher tumor grade, larger tumor size, and more nodes involved. Chemotherapy recommendation was higher for patients of younger age, with private insurance, and with higher tumor grade, size, and number of nodes involved. Black patients had significantly higher RS (AOR, 1.37; 95% CI, 1.25-1.79).Conclusions:The RS assay influences clinicians' chemotherapy recommendation in node-positive EBC. Clinicians are using the inclusion criteria of the RxPONDER trial before its final release. Black patients have higher RS, likely representing worse biology. Significant differences exist in test use and clinical implications based on race, insurance, and facility.
authors.affiliation: Departments of Internal Medicine, University of Colorado, Aurora, Colorado
authors.forename: Jagar
authors.initials: J
authors.lastname: Jasem
authors.affiliation: Departments of Radiation Oncology,  University of Colorado, Aurora, Colorado
authors.forename: Christine M
authors.initials: CM
authors.lastname: Fisher
authors.affiliation: Departments of Radiation Oncology,  University of Colorado, Aurora, Colorado
authors.forename: Arya
authors.initials: A
authors.lastname: Amini
authors.affiliation: Departments of Internal Medicine, Division of Medical Oncology, University of Colorado, Aurora, Colorado
authors.forename: Elena
authors.initials: E
authors.lastname: Shagisultanova
authors.affiliation: Departments of Radiation Oncology,  University of Colorado, Aurora, Colorado
authors.forename: Rachel
authors.initials: R
authors.lastname: Rabinovitch
authors.affiliation: Departments of Internal Medicine, Division of Medical Oncology, University of Colorado, Aurora, Colorado
authors.forename: Virginia F
authors.initials: VF
authors.lastname: Borges
authors.affiliation: Departments of Internal Medicine, Division of Medical Oncology, University of Colorado, Aurora, Colorado
authors.forename: Anthony
authors.initials: A
authors.lastname: Elias
authors.affiliation: Departments of Internal Medicine, Division of Medical Oncology, University of Colorado, Aurora, Colorado
authors.forename: Peter
authors.initials: P
authors.lastname: Kabos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D000066491:Clinical Decision-Making; D002986:Clinical Trials as Topic; D015897:Comorbidity; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016017:Odds Ratio; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor