Responses of phenotypically diverse heterogeneous cancers are complicated by different levels of PRLR isoforms with distinct signaling capabilities, selection and genomic evolution as tumors progress and respond to initial therapies, and environmental context, including site-specific responses of the metastatic niche [e.g., bone (120)], ECM properties and the steroid hormone and growth factor milieu (Figure 3). Here, PRLR is linked to cancer.