The ongoing prospective randomized study S1007 or RxPONDER (Rx for Positive Node, ER+ Breast Cancer)24 which randomizes patients with ER+/HER2− negative breast cancer with 1–3 positive lymph nodes, with RS ≤ 25 to either endocrine therapy alone or chemotherapy followed by endocrine therapy will provide prospective data on the most appropriate systemic therapy recommendations for this group. The gene discussed is ERBB2; the disease is breast carcinoma.