Many studies have shown that epigenetic changes, such as altered DNA methylation and histone modifications, are linked to estrogen receptor xcexb1 (ERxcexb1)-positive tumors and disease prognoses. Several recent studies have applied high-throughput technologies such as ChIP-seq and MBD-seq to interrogate the altered architectures of ERxcexb1 regulation in tamoxifen (Tam)-resistant breast cancer cells. However, the details of combinatorial epigenetic regulation of ERxcexb1 target genes in breast cancers with acquired Tam resistance have not yet been fully examined.