For example, cyclin D [which forms a complex with CDK4/6 (Weinberg 2007)] was suggested to operate upstream of ER (Neuman et al. 1997) and to enhance transactivation through an estrogen response element in a CDK-independent manner (Zwijsen et al. 1997; Neuman et al. 1997), whose overexpression was shown to correlate with an ER-positive status in breast cancer (Fantl et al. 1990; Courjal et al. 1996; Buckley et al. 1993). This evidence concerns the gene ESR1 and breast cancer.