In conclusion, in this analysis of prospectively-designed registry assessing distant recurrence and breast cancer death in ER+ HER2-negative breast cancer patients with N1mi or 1–3 positive nodes where the RS result has been incorporated in treatment decision making, chemotherapy-untreated patients with RS < 18 had very good clinical outcomes supporting the use of endocrine therapy alone in this population. Here, ESR1 is linked to breast cancer.