Flaxseed vs. aromatase inhibitors: breast tumor characteristics and prognosis

描述（由申请人提供）：虽然早期乳腺癌女性的10年生存率非常好，但远处复发仍然是一个严重的问题，特别是对于雌激素受体阳性的女性。因此，乳腺癌幸存者对可能提高其无复发生存率（RFS）的治疗很感兴趣。芳香酶抑制剂（AI）用于绝经后妇女，阻断外周雄激素向雌激素的转化，有效降低雌二醇，促进乳腺肿瘤增殖。然而，人工智能的使用与潮热、关节疼痛、骨质流失和心脏事件的增加有关。此外，许多乳腺肿瘤最终会对激素治疗产生抗药性。补充和替代药物（CAMs）被癌症幸存者广泛使用，以减少副作用和潜在的健康益处，并在乳腺癌幸存者中特别普遍使用。亚麻籽（FS）是一种常见的食物，经常作为膳食补充剂食用，是木脂素（一种植物雌激素）最丰富的食物来源。在实验模型中，食用亚麻籽显示出许多活性，表明亚麻籽在佐剂设置中具有潜在的益处。然而，大多数调查亚麻籽生物效应的人体研究都涉及健康女性。关于亚麻籽在乳腺癌妇女中使用的有效性和安全性的临床数据缺乏，特别是在接受人工智能治疗的妇女中。由于亚麻籽中的植物雌激素可以影响许多与激素制剂相同的生物途径，因此饮食药物相互作用是可能的。此外，亚麻籽可能通过生长和信号通路起作用，改变内分泌抗性的发展。亚麻籽和抗雌激素之间潜在的协同或拮抗作用是特别感兴趣的，因为越来越多地使用人工智能来治疗绝经后妇女的激素反应性疾病。我们建议在绝经后诊断为ER阳性乳腺癌的妇女中进行肿瘤活检和切除之间的2x2因子随机干预研究，以评估亚麻籽和AI对一些类固醇激素和与长期生存相关的肿瘤相关特征的影响，并研究亚麻籽和AI对肿瘤中Ki-67、caspase、ERa、ER¿、PgR、HER2、IGF1、IGFIR表达的潜在相互作用。术前设置提供了一个独特的机会，可以在不受其他治疗干扰的情况下，在短时间内快速获得与肿瘤特征相关的生长因子和信号通路的干预相关信息。我们假设亚麻籽和人工智能干预都能独立影响生长因子和信号通路蛋白的表达，从而减少肿瘤增殖和增加细胞凋亡。我们进一步假设，这些改善将反映在乳腺癌抗体小组（应用基因组学公司）估计的改善的复发评分中。本研究将为未来涉及亚麻籽植物雌激素木脂素的饮食干预研究提供重要的临床数据。该研究计划检验食用亚麻籽（一种富含植物雌激素的食物）与芳香化酶抑制剂相比，作为雌激素受体阳性乳腺癌的补充治疗方法的效果，以及亚麻籽和芳香化酶抑制剂联合治疗乳腺癌的效果。由于补充和替代治疗方法的使用越来越多，以及芳香化酶抑制剂在乳腺癌治疗中的应用，该研究有可能为高植物雌激素食物对乳腺癌常用内分泌治疗的影响提供重要的临床信息。

DESCRIPTION (provided by applicant): Although the 10 year survival rate for women with early stage breast cancer is very good, distant recurrence is still a serious concern, especially for estrogen receptor positive women. Consequently, breast cancer survivors are interested in therapies that might improve their recurrence free survival (RFS). Used in postmenopausal women, aromatase inhibitors (AI) block the peripheral conversion of androgens to estrogen, effectively lowering the estradiol available to promote breast tumor proliferation. However, use of AIs is associated with hot flashes, joint pain, bone loss, and an increase in cardiac events. Furthermore, many breast tumors eventually develop resistance to hormonal treatments. Complementary and alternative medicines (CAMs) are widely used by cancer survivors in an attempt to reduce disease recurrence with fewer side effects and potential health benefits, and use is particularly prevalent among breast cancer survivors. Flaxseed (FS) is a commonly available food often consumed as a dietary supplement and is the richest food source of lignans, a phytoestrogen. In experimental models, flaxseed consumption has been shown to exhibit a number of activities that suggest a potential benefit of flaxseed in the adjuvant setting. However, the majority of human studies investigating the biologic effects of flaxseed have involved healthy women. There is a paucity of clinical data regarding the efficacy and safety of use of flaxseed among women with breast cancer, especially among those receiving AIs. Because the phytoestrogens in flaxseed can influence many of the same biologic pathways affected by hormonal agents, diet-drug interactions are possible. Additionally, it is possible flaxseed could act through growth and signaling pathways, modifying the development of endocrine resistance. Potential synergistic or antagonistic effects between flaxseed and antiestrogens are of particular interest given the increasing use of AIs to treat postmenopausal women with hormone responsive disease. We propose to conduct a pilot 2x2 factorial randomized intervention study between tumor biopsy and resection, in postmenopausal women diagnosed with ER positive breast cancer, to assess the effects of flaxseed and AI on a number of steroid hormone and tumor-related characteristics associated with long-term survival, and to investigate the potential interaction between flaxseed and AI on tumor expression of Ki-67, caspase, ERa, ER¿, PgR, HER2, IGF1, IGFIR. The pre-surgical setting offers a unique opportunity to rapidly obtain information on intervention related effects on growth factor and signaling pathways related to tumor characteristics in a short time period without the interference of other treatments. We hypothesize that both flaxseed and AI interventions will independently favorably affect growth factor and signaling pathway protein expression resulting in reduced tumor proliferation and increased apoptosis. We further hypothesize that these improvements will be reflected in improved recurrence scores as estimated by the Mammostrat antibody panel (Applied Genomics Incorporated). The proposed study will provide important clinical data for future dietary intervention studies involving phytoestrogen lignans from flaxseed. The proposed study plans to examine the effect of flaxseed consumption, a phytoestrogen rich food, compared to aromatase inhibitors as a complementary approach to treating estrogen receptor positive breast cancer, as well as the effect of combined flaxseed and aromatase inhibitor therapy on breast cancer treatment. Because of the increasing use of both complementary and alternative approaches to treatment, and the of aromatase inhibitors in the treatment of breast cancer, the proposed study has potential to provide important clinical information about the effect of foods high in phytoestrogens on a common endocrine therapy used in breast cancer.