Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
Department of Population Health, University of Kansas Medical Center, Kansas City, Kansas.
Cancer Prev Res (Phila). 2021 Sep;14(9):893-904. doi: 10.1158/1940-6207.CAPR-20-0656. Epub 2021 Jul 9.
The inflammation-resolving and insulin-sensitizing properties of eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids have potential to augment effects of weight loss on breast cancer risk. In a feasibility study, 46 peri/postmenopausal women at increased risk for breast cancer with a body mass index (BMI) of 28 kg/m or greater were randomized to 3.25 g/day combined EPA and DHA (ω-3-FA) or placebo concomitantly with initiation of a weight-loss intervention. Forty-five women started the intervention. Study discontinuation for women randomized to ω-3-FA and initiating the weight-loss intervention was 9% at 6 months and thus satisfied our main endpoint, which was feasibility. Between baseline and 6 months significant change () was observed in 12 of 25 serum metabolic markers associated with breast cancer risk for women randomized to ω-3-FA, but only four for those randomized to placebo. Weight loss (median of 10% for trial initiators and 12% for the 42 completing 6 months) had a significant impact on biomarker modulation. Median loss was similar for placebo (-11%) and ω-3-FA (-13%). No significant change between ω-3-FA and placebo was observed for individual biomarkers, likely due to sample size and effect of weight loss. Women randomized to ω-3-FA exhibiting more than 10% weight loss at 6 months showed greatest biomarker improvement including 6- and 12-month serum adiponectin, insulin, omentin, and C-reactive protein (CRP), and 12-month tissue adiponectin. Given the importance of a favorable adipokine profile in countering the prooncogenic effects of obesity, further evaluation of high-dose ω-3-FA during a weight-loss intervention in obese high-risk women should be considered. PREVENTION RELEVANCE: This study examines biomarkers of response that may be modulated by omega-3 fatty acids when combined with a weight-loss intervention. While focused on obese, postmenopausal women at high risk for development of breast cancer, the findings are applicable to other cancers studied in clinical prevention trials.
二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）脂肪酸具有抗炎和胰岛素增敏作用，有可能增强减肥对乳腺癌风险的影响。在一项可行性研究中，46 名患有乳腺癌风险增加且体重指数（BMI）大于或等于 28 kg/m2 的绝经后妇女被随机分为每天 3.25 克联合 EPA 和 DHA（ω-3-FA）或安慰剂，同时开始减肥干预。45 名女性开始了干预。随机分配到 ω-3-FA 并开始减肥干预的女性中有 9%在 6 个月时停止研究，因此满足了我们的主要终点，即可行性。与随机分配到 ω-3-FA 的女性相比，基线和 6 个月时，25 个与乳腺癌风险相关的血清代谢标志物中有 12 个发生了显著变化（），而随机分配到安慰剂的女性只有 4 个发生了显著变化。体重减轻（试验启动者的中位数为 10%，完成 6 个月的 42 名女性的中位数为 12%）对生物标志物的调节有显著影响。安慰剂（-11%）和 ω-3-FA（-13%）的中位数损失相似。在 ω-3-FA 和安慰剂之间，个体生物标志物没有观察到显著变化，可能是由于样本量和体重减轻的影响。随机分配到 ω-3-FA 的女性在 6 个月时体重减轻超过 10%，表现出最大的生物标志物改善，包括 6 个月和 12 个月时的血清脂联素、胰岛素、网膜素和 C 反应蛋白（CRP）以及 12 个月时的组织脂联素。鉴于有利的脂肪因子谱在对抗肥胖的致癌作用方面的重要性，应考虑在肥胖高危女性的减肥干预中进一步评估高剂量 ω-3-FA。预防相关性：本研究检查了与减肥干预联合使用时可能被ω-3 脂肪酸调节的生物标志物。虽然该研究集中在患有乳腺癌风险增加且绝经后肥胖的高危女性，但研究结果适用于其他在临床预防试验中研究的癌症。
