Among premenopausal women with 1 to 3 nodes, the RxPONDER trial revealed up to a 5% absolute benefit of chemotherapy, regardless of genomic risk, potentially due to chemotherapy-induced ovarian failure rather than cytotoxic effects of chemotherapy.11 Premenopausal women with HR-positive, ERBB2-negative breast cancer are at higher risk for recurrence,12 but RS alone appears to be less reliable in this patient group. The gene discussed is ERBB2; the disease is breast cancer.