The disruption of this crosstalk by knockdown of IL-6 or RANK in breast cancer cells, or via treatment with anti-IL-6 receptor antibodies or an antagonist molecule, i.e., TB-2-081, significantly reduced breast cancer growth in bone [27,28,64,65], as well as in the presence of hormonal therapy (HT)-resistant metastatic disease where the anti-IL-6 receptor would block the IL-6hi/estrogen (ER)lo feed-forward loop [26]. This evidence concerns the gene TNFRSF11A and metastatic neoplasm.