Soy-rich diet for preventing chronic post breast cancer surgery pain

描述（由申请人提供）： 乳腺癌术后慢性疼痛（CPBCS）是乳腺癌女性长期发病的最常见原因，发病率高达72%。与其他慢性术后疼痛状况类似，CPBCS可能对治疗有抵抗力，并持续多年，使女性承受其身体，情感和社会后果。对人类的研究表明，采用预先镇痛的概念，即，在手术前而不是手术后使用疼痛缓解措施可能最终降低术后疼痛水平。此外，与手术后采取的相同措施相比，手术前预先使用镇痛措施可能会防止急性术后疼痛进展为慢性疼痛。富含大豆蛋白的饮食减少了啮齿动物的慢性手术后疼痛，也可能减少人类的疼痛。这种效果在手术前预先补充大豆蛋白的动物中最为明显。我们在这项随机、双盲、II期临床试验中的主要目的是测试在乳腺癌手术前预先给予女性富含大豆蛋白的饮食是否可以预防CPBCS的发展。将招募220名被诊断患有乳腺癌并计划进行乳腺癌手术的女性。试验将包括两个阶段：1.术前饮食控制阶段，将持续2周，和2。术后随访期，持续1年。在第一阶段，合格的候选人将接受基本的饮食评估，然后根据他们绝经前与绝经后的状态和计划的手术类型，即，正式乳房切除术与保乳手术。每组中的女性将随机接受大豆蛋白或牛奶蛋白：50%的每日膳食蛋白将转化为粉末状实验蛋白，实验组为大豆蛋白，对照组为牛奶蛋白。将指导女性将其每日蛋白质摄入量减少一半，以保持其饮食等能和等蛋白质，并保持相同的脂肪和碳水化合物特征。在第二个手术后阶段，妇女将恢复正常饮食。在一年的随访期间，将对参与者的疼痛水平、残疾、抑郁、体力活动和止痛药物的使用进行评估。这将在基线和术后3、6和12个月进行。我们假设一年后，食用富含大豆蛋白饮食的女性患CPBCS的人数将比食用富含牛奶蛋白饮食的女性少50%。如果被证明是有益的，这种简单的饮食操作可能会防止乳腺癌最严重的后遗症之一。乳腺癌手术后的慢性疼痛是诊断为乳腺癌的女性长期发病的最常见原因（15）。大豆产品越来越多地被东南亚以外的人群消费，因为它们被证明是安全的，可行的，并且与预防冠状动脉疾病和癌症等重大疾病有关（60，68）。在这项试验中，我们希望表明，在乳腺癌手术前食用富含大豆蛋白的饮食可能会降低术后慢性疼痛的发生率。如果得到证实，这个简单的措施可能会预防乳腺癌最严重的后遗症之一，并改善全球数百万妇女的生活质量。

DESCRIPTION (provided by applicant): Chronic pain after breast cancer surgery (CPBCS) is the most common cause for long-term morbidity in women diagnosed with breast cancer, with an incidence as high as 72%. Similar to other chronic postoperative pain conditions, CPBCS could be resistant to treatment and last for years, burdening women with its physical, emotional and social consequences. Studies in humans showed that adopting the concept of preemptive analgesia, i.e., the use of pain relieving measures prior to surgery rather than after it, may eventuate in decreased postoperative pain levels. Moreover, the preemptive use of analgesic measures prior to surgery may prevent the progression of acute postoperative pain to chronicity, compared to the same measures taken after surgery. Diets enriched with soy protein decreased chronic post surgical pain in rodents, and possible in humans. This effect was most apparent in animals when the soy protein was supplemented preemptively, prior to surgery. Our primary objective in this randomized, double blind, phase II clinical trial is to test whether diet enriched with soy protein, given to women preemptively prior to breast cancer surgery, may prevent the development of CPBCS. Two hundred and twenty women, diagnosed with breast cancer and scheduled for breast cancer surgery will be recruited. The trial will comprise two phases: 1. A preoperative dietary manipulation phase that will last for 2 weeks, and 2. A postoperative follow up period, lasting for one year. In the first phase eligible candidates will undergo a basic dietary evaluation followed by stratification into 4 study groups, based on their pre-vs. postmenopausal status and the planned type of surgery, i.e., formal mastectomy vs. breast-conserving surgery. Women in each group will be randomized to receive either the soy or milk protein: 50% of the daily dietary protein will be converted to powdered experimental proteins, soy protein in the experimental group and milk protein in the control group. Women will be instructed to decrease their daily protein consumption by half for maintaining their diet isoenergetic and isoproteic, and to maintain the same fat and carbohydrate profile. During the second, post-surgical phase women will resume their normal diet. During a one year follow up participants will be evaluated for their pain levels, disability, depression, physical activity and utilization of analgesic medications. This will be done at baseline and 3, 6, and 12 months postoperatively. We assume that after a year the number of women developing CPBCS after consuming the soy-protein enriched diet will be 50% less that women consuming milk protein-enriched diet. If shown to be beneficial, this simple dietary manipulation may prevent one of the most severe sequelae of breast cancer.Chronic pain after breast cancer surgery is the most common cause for long-term morbidity in women diagnosed with breast cancer (15). Soy products are increasingly consumed by populations outside South East Asia due to their proven safety, feasibility and their association with the prevention of major ailments like coronary artery disease and cancer (60,68). In this trial we hope to show that consumption of a diet enriched with soy protein before breast cancer surgery may decrease the incidence of chronic pain after it. If indeed proven, this simple measure may prevent one of the most severe sequelae of breast cancer and improve the quality of life of millions of women worldwide.