ESR1 and cancer: The RxPonder trial showed that chemotherapy can be safely omitted in postmenopausal patients with 1–3 positive lymph nodes with a low genomic risk score who will receive adjuvant endocrine therapy; however, systemic chemotherapy is still recommended for patients with ≥ 4 positive lymph nodes.20 Optimal systemic therapy regimens will likely continue to evolve as novel therapeutics, such as cyclin dependent kinase (CDK) 4/6 inhibitors, are used more frequently in patients with high-risk ER+ HER2 negative cancers.