Thus, progesterone opposes the estrogen–ER signaling at the DSCAM-AS-1–ESR1 genomic axis via two synergistic modes: it reduces the expression of DSCAM-AS1 and elevates the expression of miR-130a, which interacts with both DSCAM-AS1 and 3′-UTR of ESR1 in breast cancer cells. This evidence concerns the gene DSCAM and breast cancer.