During the nocturnal sleep phase, breast cancer cells are subjected to circadian-regulated hormonal fluctuations, including those of melatonin, glucocorticoids, and testosterone, that promote their shedding from proliferating tumors, which coincides with the timing of most spontaneous metastatic events.91 The circadian rhythm regulatory protein BMAL1 exerts tumor-suppressive effects in obesity-associated triple-negative breast cancer (TNBC) models by suppressing high insulin-induced mitochondrial metabolic flexibility, and its downregulation is associated with increased metastatic risk.180. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.