Women whose levels of serum ER-α and ER-β bioactivity were in the highest quintile among controls had a 7.57-(95% confidence interval (CI): 2.46–23.32; P=0.0004) and a 10.14 (95% CI: 3.19–32.23; P<0.0001)-fold risk for general and oestrogen receptor-positive breast cancer, respectively. This evidence concerns the gene ESR2 and breast cancer.