Evidence for estrogen receptor–independent mechanisms from biomarker studies includes findings of an inverse association between genistein and Ki-67 at high levels of Ki-67 expression in invasive breast cancer (68), supporting an antiproliferative effect of soy isoflavones and significant reductions in proliferation (Ki-67 labelling index), HER2 expression, and an increase in apoptosis in breast cancer with 25 g/day flaxseed (69). This evidence concerns the gene ESR1 and breast cancer.