INTRODUCTION: Oxygenated metabolites of cholesterol (“oxysterols”) can influence carcinogenesis and contribute to resistance to endocrine therapy, an effect mostly described in vitro. OBJECTIVES: We sought to establish a method for screening plasma levels of oxysterols in breast cancer patients, estimate their individual variability and detection limits, and provide basic information about their roles in tumor biology. METHOD: Liquid-chromatography coupled with tandem mass spectrometry was used for determination of levels of 25-hydroxycholesterol, 27-hydroxycholesterol, 7α-hydroxycholesterol, and 7-ketocholesterol in plasma sample pairs from patients before and 12–24 months after surgical removal of tumors (n=24). Deuterated standards of all oxysterols were used for method validation. RESULT: All oxysterols were successfully detected in patient plasma samples. A significant increase in the level of 7-ketocholesterol was observed in the samples following tumor removal and the start of therapy compared to the sampling before (p=0.002). This increase was unrelated to personal characteristics of patients, expression of estrogen receptor, or to adjuvant therapy type. CONCLUSION: This study shows, for the first time, that circulating levels of oxysterols, especially 7-ketocholesterol, may reflect the presence of tumor cells in patients.

Biomedical Centre Medical School Pilsen Charles University Pilsen Czech Republic

Department of Biochemistry Vanderbilt University School of Medicine Nashville TN USA

Department of Medicine Vanderbilt University Medical Center Nashville TN USA

Department of Oncology Palacky University Medical School and Teaching Hospital Olomouc Czech Republic

Department of Oncosurgery MEDICON Prague Czech Republic

Department of Pharmacology National Yang Ming University Taipei Taiwan

Department of Toxicogenomics National Institute of Public Health Srobarova 48 Prague 100 42 Czech Republic Phone 420 267082711

Institute of Biopharmaceutical Sciences National Yang Ming University Taipei Taiwan

National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei Taiwan

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