In postmenopausal women, higher 27HC concentrations were associated with lower risk of ERβ-negative breast cancer (ORlog2:0.31; 95%CI 0.10, 0.92; phet by menopausal status in ERβ-negative = 0.06), whereas no association was observed among ERβ-positive cases (ORlog2: 0.72 (95% CI 0.36, 1.47); phet by ERβ status in postmenopausal = 0.12) (n = 146 postmenopausal cases with ERβ data). Here, ESR2 is linked to breast cancer.