These molecules such as the adhesion molecules PD-L1 and PD-1, which mediate direct communication between tumor cells and T cells, VEGF and VEGFR, which mediate indirect cell communication in a paracrine and autocrine manner, and estrogen and estrogen receptors, which mediate indirect cell communication similar to hormone and lactic acid metabolite mediation of indirect communication in the local acidic microenvironment, are often considered to be targets in breast cancer treatment. The gene discussed is ESR1; the disease is breast cancer.