In the past 20 years, three types of molecular features emerged that predict endocrine and chemotherapy sensitivities in early stage-breast HR+/HER2− cancer; (i) expression of estrogen receptor (ER) regulated genes is a measure of endocrine sensitivity and is associated with better prognosis15, (ii) proliferation, and (iii) immune infiltration related markers are independently associated with greater chemotherapy sensitivity in neoadjuvant chemotherapy trials16–18. The gene discussed is ESR1; the disease is cancer.