Third, β2M exhibits different regulatory effects on CREB and p-CREB in the cell lines of ER+ breast cancer with HER2− (MCF-7 and T47D), and HER2 and Bcl-2 in the cell lines of ER− breast cancer with HER2− (MDA-MB-231 and Hs578T), which may be due to the fact that breast cancer has a very complex molecular regulatory mechanism, and every type of breast cancer has several subtypes, and these signaling molecules may be regulated by other pathways in corresponding subtypes of breast cancer. This evidence concerns the gene ESR1 and breast cancer.