In a study reported in NEJM Evidence, Joseph A. Sparano, MD, and colleagues found that a risk score integrating the 21-gene recurrence score (RS) with clinicopathologic factors—the RSClin tool—performed well in predicting risk of late distant recurrence in patients with breast cancer.
Joseph A. Sparano, MD
Study Details
The RSClin tool integrates the RS with the clinicopathologic factors of histologic grade, tumor size, and age at surgery. In the study, a patient-specific meta-analysis including 10,004 women with hormone receptor–positive, HER2-negative, axillary node–negative disease from three clinical trials, used to establish the tool, was updated using extended follow-up data from the TAILORx trial.
Likelihood ratio (LR) tests were used to compare prognostic findings for late distant recurrence with the RSClin tool model with models using only clinicopathologic factors or only the RS. External validation of the updated RSClin tool prognosis for distant recurrence used data from an independent cohort of 1,098 patients from the real-world Clalit Health Registry.
Key Findings
Comparison of likelihood ratio tests using the updated data set, including longer follow-up and more events, showed that the RSClin model provided significantly improved estimates of risk of late distant recurrence vs the model with tumor grade, tumor size, and age (ΔLR chi-square test = 86.2, P < .001) and the model with RS alone (ΔLR chi-square test = 131.0, P < .001).
In the independent cohort, the updated RSClin model was prognostic for distant recurrence by 10 years after diagnosis (standardized hazard ratio [HR] = 1.56, 95% confidence interval [CI] = 1.25–1.94), with the estimated risk closely approximating the observed 10-year risk (Lin concordance = 0.87). The model was prognostic for late distant recurrence at 5 years (standardized HR = 1.78, 95% CI = 1.25–2.55), with the estimated risk closely approximating observed risk (Lin concordance = 0.92).
The investigators concluded, “The 21-gene RS is prognostic for distant recurrence and overall survival in early breast cancer. A model integrating the 21-gene RS and clinicopathologic factors improved estimates of distant recurrence risk compared with either used individually and stratified late distant recurrence risk.”
Dr. Sparano, of the Icahn School of Medicine at Mount Sinai, New York, is the corresponding author for the NEJM Evidence article.
Disclosure: The study was funded by the National Cancer Institute and others. For full disclosures of the study authors, visit evidence.nejm.org.
