While the 21-gene expression assay is useful in gauging the potential benefit of prescribing cytotoxic chemotherapy in high-risk cases, its utility in estimating LRR risk is less apparent: Tumor blocks retrieved from the NSABP-B14 and B20 trials were evaluated with the sole purpose of establishing the risk of distant disease recurrence in a subset of ER+/HER2− lymph node-negative (LN-) breast cancer patients, before being combined to develop the RS signature [5]. The gene discussed is ESR1; the disease is breast cancer.