Prospective cohort study of circulating 27-hydroxycholesterol, sex steroid hormones, and risk of mortality in postmenopausal breast cancer

Biomarkers in the hormonal and metabolic pathways linking obesity and mortality can influence survival after breast cancer diagnosis. The Multiethnic Cohort study (1993-2017) prospectively investigated associations with mortality for prediagnostic plasma levels of circulating 27-hydroxycholesterol (27HC), estrone, testosterone, and sex hormone binding globuline (SHBG) measured on average 6.7 years before breast cancer diagnosis in 1009 postmenopausal women not using menopausal hormone therapy at blood draw. Over an average follow-up of 7.8 years (SD 4.2), 300 deaths occurred, including 83 breast cancer –specific deaths. Inverse associations were found for 27HC (highest versus lowest tertile HR 0.73; 95% CI 0.54-0.98) with all-cause but not breast cancer-specific mortality, and estrone (0.37; 0.20-0.70) with breast cancer-specific but not all-cause mortality; SHBG was positively associated with all-cause (1.76; 1.28-2.41) but not breast cancer-specific mortality. No associations were found for testosterone. There was no statistically significant heterogeneity in associations by body mass index, estrogen receptor status, or race and ethnicity. The authors conclude that this analysis found associations for prediagnostic 27HC, estrone, and SHBG with mortality.