Buechler SA, et al. - Researchers assessed the ability of EarlyR (a gene signature that uses ESPL1, SPAG5, MKI67, PLK1 and PGR to classify ER+ breast cancer [ER+ BC] into EarlyR-Low, EarlyR-Int, and EarlyR-High risk strata and is prognostic in patients treated with adjuvant chemotherapy) to predict pathological complete response (pCR) and long-term survival after neoadjuvant chemotherapy (NACT). They used publicly available Affymetrix microarray datasets (Cohort A; n = 659; 74 pCR events) derived from NACT-treated ER+ BC patients. In patients treated with NACT and adjuvant hormone therapy (AHT) (n = 281), they assessed distant relapse-free survival (DRFS) results. They compared these results with patients treated with AHT alone (n = 455) (Cohort B; n = 736; 142 events). Findings revealed a robust link between high EarlyR and pCR in patients treated with neoadjuvant chemotherapy. For patients in EarlyR-High not receiving NACT, poor DRFS outcomes were predicted by EarlyR. It also improved survival in NACT-treated EarlyR-High patients. Overall, findings established the ability of EarlyR to serve as a prognostic assay and a predictive assay that identifies patients, who are also likely to respond to chemotherapy.