芬列奈德,一种在乳腺中积累的低毒性的类维生素A,已被证明可以预防年轻女性的第二次乳腺癌。芬列奈德具有凋亡和抗侵袭性,可改善患有胰岛素抵抗的超重绝经前妇女的胰岛素敏感性。这项研究旨在通过测量与胰岛素敏感性和乳腺癌风险相关的循环生物标志物来进一步表征其在癌症预防中的作用。62个女人,年龄在20到46岁之间,健康或已经接受过乳腺癌手术的人,根据BRCAPRO模型,已知BRCA1/2突变或突变可能性≥20%,被随机分配接受fenretinide(200mg/天)或安慰剂5年(试验注册:EudraCTNo.2009-010260-41).在基线时抽取空腹血样,12个月和36个月,并分析了以下生物标志物:视黄醇,瘦素,脂联素,视黄醇结合蛋白4(RBP-4),总胆固醇,高密度脂蛋白(HDL)和低密度脂蛋白(LDL)胆固醇,甘油三酯,葡萄糖,胰岛素,胰岛素样生长因子(IGF-1),IGF结合蛋白3,性激素结合球蛋白(SHBG),睾丸激素,血管内皮生长因子(VEGF)。经过12个月的治疗,我们观察到fenretinide对葡萄糖的有利作用(降低;P=0.005),胰岛素(减少;P=0.03),稳态模型评估指数(下降;P=0.004),HDL胆固醇(增加;P=0.002),即使这些影响在36个月后不太明显。视黄醇和视黄醇结合蛋白4在整个研究中显著降低(P<0.0001)。其他测量的生物标志物都没有改变。
■Fenretinide对代谢谱具有有益作用,支持其在乳腺癌预防中的临床应用,特别是在具有阳性家族史和BRCA1/2基因致病变异的绝经前妇女中。这一发现需要在更大的试验中进行进一步的研究,以证实其在乳腺癌预防中的作用。
Fenretinide, a retinoid with a low-toxicity profile that accumulates in the breast, has been shown to prevent second breast cancer in young women.
Fenretinide exhibits apoptotic and antiinvasive properties and it improves insulin sensitivity in overweight premenopausal women with insulin resistance. This study aimed to further characterize its role in cancer prevention by measuring circulating biomarkers related to insulin sensitivity and breast cancer risk.Sixty-two women, ages 20 to 46 years, healthy or who had already undergone breast cancer surgery, with a known BRCA1/2 mutation or a likelihood of mutation ≥20% according to the BRCAPRO model, were randomly assigned to receive
fenretinide (200 mg/day) or placebo for 5 years (trial registration: EudraCT No. 2009-010260-41). Fasting blood samples were drawn at baseline, 12 and 36 months, and the following biomarkers were analyzed: retinol, leptin, adiponectin, retinol-binding protein 4 (RBP-4), total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, glucose, insulin, insulin-like growth factor (IGF-1), IGF-binding protein 3, sex hormone binding globulin (SHBG), testosterone, and vascular endothelial growth factor (VEGF).After 12 months of treatment, we observed a favorable effect of
fenretinide on glucose (decrease; P = 0.005), insulin (decrease; P = 0.03), homeostatic model assessment index (decrease; P = 0.004), HDL cholesterol (increase; P = 0.002), even though these effects were less prominent after 36 months. Retinol and retinol-binding protein 4 markedly decreased (P < 0.0001) throughout the study. None of the other measured biomarkers changed.
UNASSIGNED: Fenretinide exhibits beneficial effects on the metabolic profile, supporting its clinical use in breast cancer prevention especially in premenopausal women with a positive family history and pathogenic variants in BRCA1/2 genes. This finding requires further investigations in larger trials to confirm its role in breast cancer prevention.