In endocrine therapy-resistant breast cancer, Notch signaling is dysregulated, promoting resistance through mechanisms such as regulation of ER expression, interaction with other resistance pathways, modulation of tumor macrophage differentiation, increase in the BCSC-to-mesenchymal cell ratio, alteration of the tumor microenvironment, and influence on the cell cycle (Bai et al., 2020; BeLow and Osipo, 2020). The gene discussed is ESR1; the disease is breast cancer.