The New Primary Endocrine-Therapy Origination Study (NEOS), a phase 3 trial initiated in 2008, evaluated disease-free survival of postmenopausal patients with ER+, HER2-negative, node-negative, non-metastatic primary breast cancer who were randomized to adjuvant hormonal therapy with or without chemotherapy based on clinical response (CR, PR, or stable disease [SD]) to 24–28 weeks of neoadjuvant letrozole treatment. The gene discussed is ESR1; the disease is breast cancer.