Despite these limitations, this study establishes that a subset of clinically and genomically high-risk, ER+HER2– breast cancers are highly sensitive to IO and using a specific and sensitive selection strategy, patients could achieve pCR rates similar to those achieved with the most effective neoadjuvant chemotherapies in TNBC and HER2+ cancers (ie, pCR rate >65%-70%). The gene discussed is ESR1; the disease is breast carcinoma.