When analyzing breast cancer gene alterations, researchers have discovered that the JAK2 and STAT3 pathway components undergo several nonsense substitutions, splice site mutations, and frameshift indels, resulting in the inactivation of the pathway both in ER+ and triple-negative cancers; even though the primary tumor cells lacked the aforementioned changes, it still led to metastasis [138]. This evidence concerns the gene ESR1 and breast cancer.