Inhibition of ER activity with anti-estrogens or aromatase inhibitors (AI) for preventing estrogen biosynthesis, reduces relapse and improves patient survival.1, 2 However, in many patients tumours progress on these therapies, where resistant tumours are mostly ER-positive and frequently responsive to changes in endocrine agent,3, 4, 5, 6 although typically with shorter periods of response to second and third line endocrine treatments. The gene discussed is ESR1; the disease is neoplasm.