34P Premenopausal breast cancer and CYP27A1 expression: A cholesterol-associated biomarker

An important link between hypercholesterolemia and breast cancer (BC) prognosis may be the cholesterol metabolite 27-hydroxycholesterol (27HC) acting as an estrogen receptor (ER) ligand and catalysed by the CYP27A1 enzyme. This study aimed to investigate the prognostic value of CYP27A1 expression in a large population-based cohort of premenopausal women with BC. We included 4,684 premenopausal women diagnosed with stage I-III BC between 2002-2011 and registered in the Danish Breast Cancer Group clinical database. We assessed CYP27A1 expression using immunohistochemistry on tissue microarrays. CYP27A1-expression was categorized in four intensity levels: 0(absent), 1(weak), 2(moderate), 3(strong), and dichotomized into low (0,1) and high(2,3). We followed patients from date of BC primary surgery to the first of BC recurrence, death, emigration, or 10 years of follow up. We evaluated the association of CYP27A1-expression with BC recurrence and mortality using Cox regression estimating hazard ratios (HR) and associated 95% confidence intervals (95%CI) adjusting for patient, tumor, and treatment characteristics. Tumor expression of CYP27A1 was successfully assessed in 4,241 patients with a median follow-up of 7.5 years, during which 787 disease-free survival (DFS) events occurred. Tumors with high CYP27A1-expression occurred more frequently among patients with younger age at diagnosis, higher histological grade, ER negativity, progesterone receptor negativity and HER2 normality. Overall, there was little evidence of an association between CYP27A1-expression and DFS in the entire cohort (HRadj 0.90 95%CI 0.72-1.11) or in the ER-positive subgroup (n=3,330) (HRadj 0.92 95%CI 0.71-1.19). High CYP27A1-expression was associated with improved DFS among patients with ER-negative tumors (n=911): (HRcru 0.69 95%CI 0.53-0.89). The adjusted analyses showed similar, although less precise estimates (n=492): (HRadj 0.82 95%CI 0.55-1.21. High tumor CYP27A1-expression may be associated with improved prognosis among premenopausal ER-negative BC patients. This association needs testing in larger cohorts, preferably containing both pre- and postmenopausal patients.