Interactive Effects of Flaxseed and Tamoxifen in Breast*

描述（由申请人提供）：他莫昔芬（TAM）是一种雌激素受体（ER）（+）乳腺癌女性的辅助治疗药物，作为雌激素拮抗剂。服用TAM的妇女报告说，使用补充性膳食补充剂，包括富含植物雌激素的食物，如大豆和亚麻籽，以减少肿瘤生长和复发以及TAM引起的更年期症状。然而，TAM和亚麻籽对ER（+）乳腺癌的相互作用尚未在动物或人类模型中进行过测试。因此，本研究的长期目标是确定亚麻籽是否可以增强绝经前和绝经后妇女中TAM的肿瘤抑制作用。具体目标是：（1）确定在高或低浓度雌激素存在下，亚麻籽和TAM单独和组合对人ER（+）乳腺癌（即MCF-7）生长的影响，和（2）确定一些机制。研究计划是向卵巢切除的无胸腺小鼠注射MCF-7细胞，植入含有1.7 mg雌二醇（E2）的颗粒，然后用基础饲料（BD）喂养它们。在实验1中，在肿瘤已经建立的第5周，E2颗粒将被移除并被新的颗粒取代（以模拟绝经前妇女的高E2水平）。然后将小鼠随机分为7组，使其具有相似的平均肿瘤大小：第1、4和7组喂食BD，第2和5组喂食5%亚麻籽，第3和6组喂食10%亚麻籽。第4、5和6组还将接受TAM（5 mg）颗粒植入。第7组将不替换E2（阴性对照）。在实验2中，计划与实验1相同，不同之处在于在第5周，在随机分配至7组之前，将从所有小鼠中取出现有的E2颗粒（以模拟绝经后女性的低E2水平）。第7组将更换E2（阳性对照）。在两个实验中，每周测量可触及的肿瘤，并在第20周切除肿瘤进行分析，以探索潜在的机制，包括细胞增殖、凋亡、血管生成、ER和生长因子的表达。

DESCRIPTION (provided by applicant): Tamoxifen (TAM) is an adjuvant therapy for women with estrogen receptor (ER) (+) breast cancer, acting as an estrogen antagonist. Women taking TAM report the use of complementary dietary supplements including phytoestrogen-rich foods such as soy and flaxseed to reduce tumor growth and recurrence and TAM-induced menopausal symptoms. However, the interactive effects of TAM and flaxseed on ER(+) breast cancer has not been tested in animal or human models. Therefore the long term objective of this study is to determine whether flaxseed can enhance the tumor inhibitory effect of TAM in both premenopausal and postmenopausal women. The specific aims are: (1) to determine the effect of flaxseed and TAM, alone and in combination, on the growth of human ER(+) breast cancer (i.e. MCF-7), in the presence of high or low concentrations of estrogen and (2) to determine some of the mechanisms. The study plan is to inject ovariectomized athymic mice with MCF-7 cells, implant them with a pellet containing 1.7 mg estradiol (E2), and then feed them with basal diet (BD). In Experiment 1, at week 5 when the tumors are already established, the E2 pellet will be removed and replaced by a new one (to simulate high E2 levels in premenopausal women). The mice will then be randomized into 7 groups such that they have similar mean tumor size: Groups 1, 4 and 7 will be fed the BD, Groups 2 and 5, the 5 % flaxseed, groups 3 and 6, the 10% flaxseed. Groups 4, 5 and 6 will also receive an implant of TAM (5 mg) pellet. Group 7 will not have E2 replaced (negative control). In Experiment 2, the plan is the same as in Experiment 1 except that at week 5, the existing E2 pellet will be removed from all mice (to simulate low E2 levels in postmenopausal women) before randomization to 7 groups. Group 7 will have the E2 replaced (positive control). In both experiments, palpable tumors will be measured weekly and at week 20, will be excised for analysis to explore potential mechanisms, including cell proliferation, apoptosis, angiogenesis, expression of ER and growth factors.