The 21 gene recurrence score (RS)6,16 has been determined to be prognostic in both node negative and node positive ER+/HER2− breast cancer.16–20 Additionally, the RS has been studied in secondary analysis of prospective clinical trials which tested the benefit of adjuvant chemotherapy and provides limited evidence that RS is predictive of chemotherapy benefit in node positive ER+/HER2− breast cancer patients.17–22 Based on these studies, NCCN guidelines recommends the use of the RS in decision making in the setting of both node negative and node positive (1–3 lymph nodes) ER+ breast cancer. Here, ESR1 is linked to breast cancer.