In a prospective German study including 366 assessable patients with ER(+), HER2(-) early breast cancer and 0–3 positive lymph nodes (244 patients with pN0 disease), treatment recommendations changed in 33% of all patients (pN0 30%, pN1 39%), and compared to overall pre-RS assay recommendations, 33% (pN0 29%, pN1 38%) fewer patients actually received chemotherapy in the end [12]. This evidence concerns the gene ESR1 and breast cancer.