ET has also been shown to increase paracrine levels of IL-6 and enrich for a metabolically-dormant, ET-resistant CD133high/ERlow/IL-6high cancer stem-cell population; blockade of IL-6 receptor restores ET-sensitivity via re-expression of the estrogen receptor, suggesting IL-6 as a driver of ET-resistance and therefore an attractive target in patients with ER+ MBC that is resistant to AI12. This evidence concerns the gene ESR1 and cancer.