ESR1 and breast cancer: Figure 6 shows the major mechanistic pathways from in vivo / in vitro experiments. The most important factor and pathway for Pb elevation and the pathogenesis of BC is ER signaling. Pb can activate ERα to direct the estrogen target genes expression and the BC cell reproduction (116). Moreover, Pb is a nonessential metal that can imitate or obstruct the function of essential metals to induce toxicity associated with BC (155, 156).