BecauseCCN5 is an estrogen response gene in ER-α-positive BC cells25 and present studies showed that theestradiol-treatment is able to activate CCN5 transcription in hrCCN5-treated TNBCcells (Figure 6), we conceived the possibility of aautocrine-paracrine feedback signaling loop between CCN5 and ER-α for theregulation of these molecules in both normal and cancer epithelial cells of mouse andhuman breasts with different functional perspectives. The gene discussed is ESR1; the disease is cancer.