Second, and most notable, gene set enrichment analysis of the common fulvestrant resistant gene expression signature (cluster 5) revealed significant overlap with gene sets associated with estrogen receptor negative human breast cancers, with estradiol responsiveness, and with anti-endocrine drug resistance to tamoxifen [25], [26], [27], fulvestrant [26] and aromatase inhibitors [25] in multiple breast cancer cell lines including long-term estrogen-deprived (LTED) cells [24]. This evidence concerns the gene ESR1 and breast cancer.