Although tamoxifen has been widely used for the treatment of patients with ER+ breast cancer since 1977, resistance to this drug is frequently found in patients during and after the standard regimen duration, and recent evidence has suggested intratumor heterogeneity as one of the causes of therapeutic resistance in breast cancer (Osborne, 1998; Babayan et al., 2013; Knox et al., 2014). Here, ESR1 is linked to breast cancer.