We observed limited evidence of heterogeneity in associations between circulating 27HC and breast cancer risk by tumor tissue expression of CYP27A1, CYP7B1, LXR-β, and ERβ, with the exception of statistically significant heterogeneity by LXR-β status in the subgroup of women perimenopausal at blood collection (p = 0.02). Here, CYP7B1 is linked to breast cancer.