Breast cancer accounts for 25% of the world cancers and is the most frequent cancer among women. Less developed regions had 883,000 breast cancer cases whereas more developed regions had 794,000 breast cancer cases. It is second most prevalent cancer and ranks fifth with respect to overall cancer related mortality, with a prediction of increase in new cases upto 22 million in two decades. Long-time fertility, use of oral contraceptives, nulliparity, obesity post menopause, hormone replacement therapy, various genetical, environmental and life style factors are some of the important risk factors reported. Various signaling pathways are interconnected during breast carcinogenesis. Hippo signaling actively participates in the normal mammary gland development and is an emerging tumor suppressor pathway. Deregulation of Hippo signaling leads to mammary gland malignancy. A considerable percentage of human breast cancers may be transformed due to the deregulation of Leukemia inhibitory factor receptor (LIFR). LIFR, also known as glycoprotein-190 (gp 190), is a novel tumor suppressor and belongs to the large family of the hematopoietin receptors. A variety of hematopoietic and epithelial cells has been identified for the presence of LIFR. Leukemia inhibitory factor (LIF) is a pluripotent cytokine with heterogeneous effects on hematopoietic and epithelial cells. The effects can be growth-stimulatory or growth-inhibitory based on the nature of the target cell. Several human malignancies have shown the involvement of LIFR including medulloblastoma, nasopharyngeal carcinoma, liver, lung, and breast cancer.