While the physiological role of PRL/PRLR in mammary epithelial cellular differentiation is well known, we aimed here to evaluate the impact of loss of PRLR expression in regulating plasticity and tumorigenesis of the breast cancer subtypes HR+ (MCF-7 cells) and HER2-E (SKBR-3 cells) using CRISPR/Cas9 technology. This evidence concerns the gene PRL and breast cancer.