Stearoyl-CoA desaturase-1, a novel target of omega-3 fatty acids for reducing breast cancer risk in obese postmenopausal women

Background/Objectives:Conversion of saturated fatty acids to monounsaturated fatty acids by the enzyme stearoyl-Co-A-desaturase (SCD-1) is emerging as a major factor in promoting carcinogenesis including breast cancer. The aim of our study was to explore the regulation of SCD-1 by Raloxifene and omega-3 fatty acids in women at increased risk of breast cancer based on high breast density.Subjects/Methods:As a reflection of SCD-1 activity, we measured the ratios of palmitoleic acid (C16:1n7) to palmitic acid (C16:0) (SCD-16) and oleic acid (C18:1n9) to steric acid (C18:0) (SCD-18) in plasma samples of postmenopausal women enrolled in our clinical trial (NCT00723398) designed to test the effects of the antiestrogen, Raloxifene and/or the omega-3 preparation Lovaza, on breast density, a validated biomarker of breast cancer risk.Results:We report that Lovaza but not Raloxifene-reduced SCD-16 and SCD-18 for the 2-year duration of the trial. Importantly, decreasing levels of SCD-16 and SCD-18 were associated with a progressive reduction in breast density but only in obese women (body mass index ≥ 30).Conclusions:Body mass index-related factors play an important role in the reduction of breast density and hence breast cancer risk by omega-3 fatty acids. SCD-1 may be a useful biomarker in future clinical trials testing the benefit of nutritional interventions in reducing obesity-associated breast cancer risk.