Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Premenopausal Women.
Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Premenopausal Women.
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DOI：
10.1158/1940-6207.capr-14-0335
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发表时间：
2015-10
期刊：
影响因子：
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通讯作者：
Hursting SD
中科院分区：
文献类型：
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作者：
Fabian CJ;Kimler BF;Phillips TA;Box JA;Kreutzjans AL;Carlson SE;Hidaka BH;Metheny T;Zalles CM;Mills GB;Powers KR;Sullivan DK;Petroff BK;Hensing WL;Fridley BL;Hursting SD
与omega-6花生四烯酸（AA）相比，摄入较高的omega-3二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）与降低绝经前乳腺癌的风险有不同程度的关联。本试验的目的是在设计安慰剂对照IIB期试验之前，评估高剂量EPA和DHA对血液和良性乳腺组织风险生物标志物的可行性和影响。经基线随机乳晕周围细针抽吸有增生±非典型增生证据的绝经前妇女，每天给予EPA 1860 mg + 1500mgofdha乙酯，持续6个月。在研究前的同一月经周期阶段和末次给药后的中位数3周取样血液和良性乳腺组织。在最后一次给药24小时内获得额外的血液。可行性，预先定义为50%的吸收、85%的保留和70%的遵从，被证明为46%的吸收、94%的完成和85%的遵从。红细胞磷脂中EPA + DHA与AA的比值增加，但血液激素、脂肪因子和细胞因子没有变化，细胞异型性从77%下降到38% (P = 0.002)， Ki-67中位数从2.1%下降到1.0% （P = 0.021）。探索性乳腺蛋白质组学评估显示，参与激素和细胞因子信号传导的几种蛋白质减少，对AKT/ mtor通路的影响混合。在绝经前妇女的安慰剂对照试验中，EPA加dhaa预防乳腺癌的进一步研究是有必要的。
Higher intakes of the omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid (AA) have been variably associated with reduced risk of premenopausal breast cancer. The purpose of this pilot trial was to assess feasibility and explore the effects of high-dose EPA and DHA on blood and benign breast tissue risk biomarkers before design of a placebo-controlled phase IIB trial. Premenopausal women with evidence of hyperplasia ± atypia by baseline random periareolar fine needle aspiration were given 1860 mg of EPA + 1500mgofDHAethyl esters daily for 6 months. Blood and benign breast tissue were sampled during the same menstrual cycle phase prestudy and a median of 3 weeks after last dose. Additional blood was obtained within 24 hours of last dose. Feasibility, which was predefined as 50% uptake, 85% retention, and 70% compliance, was demonstrated with 46% uptake, 94% completion, and 85% compliance. Cytologic atypia decreased from 77% to 38% (P = 0.002), and Ki-67 from a median of 2.1% to 1.0% (P = 0.021) with an increase in the ratio of EPA + DHA to AA in erythrocyte phospholipids but no change in blood hormones, adipokines, or cytokines. Exploratory breast proteomics assessment showed decreases in several proteins involved in hormone and cytokine signaling with mixed effects on those in the AKT/mTORpathways. Further investigation of EPA plusDHAfor breast cancer prevention in a placebo-controlled trial in premenopausal women is warranted.