Validation of the RSClin risk calculator in the National Cancer Data Base.

BACKGROUND:Guidelines recommend the use of genomic assays such as OncotypeDx to aid in decisions regarding the use of chemotherapy for hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer. The RSClin prognostic tool integrates OncotypeDx and clinicopathologic features to predict distant recurrence and chemotherapy benefit, but further validation is needed before broad clinical adoption. METHODS:This study included patients from the National Cancer Data Base (NCDB) who were diagnosed with stage I-III HR+/HER2- breast cancer from 2010 to 2020 and received adjuvant endocrine therapy with or without chemotherapy. RSClin-predicted chemotherapy benefit was stratified into low (<3% reduction in distant recurrence), intermediate (3%-5%), and high (>5%). Cox models were used to model mortality adjusted for age, comorbidity index, insurance, and race/ethnicity. RESULTS:A total of 285,441 patients were identified for inclusion from the NCDB, with an average age of 60 years and a median follow-up of 58 months. Chemotherapy was associated with improved overall survival only for those predicted to have intermediate (adjusted hazard ratio [aHR], 0.68; 95% confidence interval [CI], 0.60-0.79) and high benefit per RSClin (aHR, 0.66; 95% CI, 0.61-0.72). Consistent benefit was seen in the subset with a low OncotypeDx score (<26) and intermediate (aHR, 0.66; 95% CI, 0.53-0.82) or high (aHR, 0.71; 95% CI, 0.58-0.86) RSClin-predicted benefit. No survival benefit with chemotherapy was seen in patients with a high OncotypeDx score (≥26) and low benefit per RSClin (aHR, 1.70; 95% CI, 0.41-6.99). CONCLUSIONS:RSClin may identify high-risk patients who benefit from treatment intensification more accurately than OncotypeDx, and further prospective study is needed.