Women with ⩾42.1 pg ml−1 serum ER-α bioactivity and >53 pg ml−1 ER-β serum bioactivity had a 2.47-(95% CI: 1.17–5.20) and 2.34 (95% CI: 1.33–4.13)-fold risk for breast cancer and 2.70-(95% CI: 1.23–5.90) and 2.31 (95% CI: 1.27–4.22)-fold risk for ER-positive breast cancer, respectively. Here, ESR2 is linked to breast cancer.