ESR1 and breast cancer: Case ERLR_20 harbored an enriched nonsense mutation in ARID1A. ARID1A alterations are associated with more unfavorable tumor features in breast cancer and have recently been shown to determine luminal identity and therapy response in ER-positive tumors—consistent with the more basal-like transcriptional features we observe with ESR1-depleted recurrences [62–65].