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.
Keywords: breast cancer; estrogen; oxysterols; plasma; therapy.