Moreover, in addition to the approximately 20–30% of women with clinically ER- breast cancers who will not respond to endocrine agents due to the lack of a therapeutic target, 25–50% of initially ER+ breast cancers also exhibit de novo resistance to anti-oestrogens; this proportion is even more important in patients after previous failure of endocrine treatment [72,73]. The gene discussed is ESR1; the disease is breast cancer.