Effect of fenretinide and low-dose tamoxifen on insulin sensitivity in premenopausal women at high risk for breast cancer.
Effect of fenretinide and low-dose tamoxifen on insulin sensitivity in premenopausal women at high risk for breast cancer.
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DOI：
10.1158/0008-5472.can-08-0553
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发表时间：
2008-11-15
期刊：
影响因子：
11.2
通讯作者：
Decensi A
中科院分区：
文献类型：
--
作者：
Johansson H;Gandini S;Guerrieri-Gonzaga A;Iodice S;Ruscica M;Bonanni B;Gulisano M;Magni P;Formelli F;Decensi A
代谢综合征的患病率随着全球乳腺癌发病率的增加而沿着增加。由于芬维A胺改善胰岛素抵抗肥胖小鼠的胰岛素作用和葡萄糖耐量，并且因为他莫昔芬已经显示出调节参与代谢综合征的几个标志物，我们试图研究低剂量的芬维A胺或他莫昔芬对绝经前乳腺癌风险女性中与胰岛素抵抗相关的特征的影响。我们将235名女性随机分为低剂量他莫昔芬（5 mg/天）、芬维A胺（200 mg/天）、二者联合或安慰剂组，为期两年。我们采用稳态模型评估（HOMA;空腹胰岛素 * 葡萄糖/22.5）来估计胰岛素敏感性。当HOMA从≥2.8变为<2.8时，女性被认为改善了胰岛素敏感性。芬维A胺或他莫昔芬对HOMA总体无影响，但超重女性（体重指数≥25 kg/m2）在芬维A胺治疗2年后，HOMA正常化的概率高7倍（OR=7.0; 95%CI：1.2-40.5），25%的女性改善了胰岛素敏感性，而他莫昔芬使胰岛素敏感性降低了近7倍（OR=0.15; 95%CI：0.03-0.88）。在这一组中，只有5%的人改善了他们的胰岛素敏感性。有趣的是，患有上皮内或微浸润性肿瘤的女性的HOMA（3.0）高于未受影响的受试者（2.8; P=0.07）。芬维A胺可以积极平衡超重绝经前妇女的代谢特征，这可能会有利地影响乳腺癌的风险。此外，在建议使用他莫昔芬预防乳腺癌之前，应考虑代谢综合征的特征。这些结果的临床意义需要进一步的调查。
The prevalence of metabolic syndrome is increasing along with breast cancer incidence worldwide. Since fenretinide improves insulin action and glucose tolerance in insulin-resistant obese mice and because tamoxifen has shown to regulate several markers involved in metabolic syndrome, we sought to investigate the effect of fenretinide or tamoxifen at low-dose on features linked to insulin resistance in premenopausal women at-risk for breast cancer. We randomized 235 women to low-dose tamoxifen (5 mg/daily), or fenretinide (200 mg/daily), or their combination or placebo for two years. We employed the homeostasis model assessment (HOMA; fasting insulin*glucose/22.5) to estimate insulin sensitivity. Women were considered to improve insulin sensitivity when they shifted from a HOMA ≥2.8 to <2.8. There was no effect of fenretinide or tamoxifen on HOMA overall, but overweight women (body mass index ≥25 kg/m2) had a 7-fold greater probability to normalize HOMA after two years of fenretinide treatment (OR=7.0; 95%CI: 1.2-40.5), with 25% of women improving their insulin sensitivity, whereas tamoxifen decreased insulin sensitivity by almost 7 times as compared to subjects not taking tamoxifen (OR=0.15; 95%CI: 0.03-0.88). In this group only 5% improved their insulin sensitivity. Interestingly, women with intraepithelial or microinvasive neoplasia had higher HOMA (3.0) than unaffected subjects (2.8; P=0.07). Fenretinide can positively balance the metabolic profile in overweight premenopausal women and this may favorably affect breast cancer risk. Furthermore, features of the metabolic syndrome should be taken into consideration before proposing tamoxifen for breast cancer prevention. The clinical implications of these results require further investigations.