LEP and breast cancer: The following mechanisms are possible explanations for this association: Leptin activates janus tyrosine kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) and cAMP response element (CRE) signaling pathways to upregulate cyclin D1, and downregulates cyclin-dependent kinase inhibitor p21 expression, which decrease cells in G0/G1 phase and increase cells in S phase in BC to promote BC cell proliferation and regulate apoptosis [33].