As the antagonistic relationship between PRLR expression and CCN2 is observed in large breast cancer datasets and PRLR/Hippo gene signature marks breast cancer patients with favorable prognosis, therefore, we hypothesized that PRL along with agents that block YAP-CCN2 cascade could have value as single and/or combination therapies in breast cancer through restoration of differentiation and thereby limiting tumor cell growth. This evidence concerns the gene PRLR and breast cancer.