Flaxseed vs. aromatase inhibitors: breast tumor characteristics and prognosis

亚麻籽与芳香酶抑制剂：乳腺肿瘤特征和预后

• 批准号: 7586719
• 负责人: Susan E McCann
• 金额: $ 23.12万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7586719
• 关键词: Adjuvant; Adverse effects; Affect; Androgens; Androstenedione; Antibodies; Apoptosis; Apoptotic; Aromatase; Aromatase Inhibitors; Arthralgia; Biological Markers; Biopsy; Cancer Survivor; Cardiac; Caspase; Characteristics; Cholesterol; Clinical Data; Complementary and alternative medicine; Consumption; Data; Development; Diagnosis; Diet; Dietary Intervention; Disease; Distant; Drug Interactions; ERBB2 gene; Endocrine; Estradiol; Estrogen Antagonists; Estrogen Receptor Modulators; Estrogen receptor positive; Estrogens; Estrone; Event; Excision; Excretory function; Exhibits; Experimental Models; Flax; Food; Future; Genomics; Growth; Growth Factor; Health Benefit; Hormonal; Hormone Responsive; Hormones; Hot flushes; Human; Hydroxysteroid Dehydrogenases; IGF1 gene; IGFBP3 gene; Intervention; Intervention Studies; Lignans; Mammary Neoplasms; Menopause; Minerals; Neoadjuvant Therapy; Neoplasm Metastasis; Operative Surgical Procedures; Pathway interactions; Peripheral; Pharmaceutical Preparations; Phytoestrogens; Postmenopause; Radiation; Randomized; Recurrence; Resistance; Resistance development; SHBG gene; Safety; Sampling; Serum; Signal Pathway; Somatotropin; Source; Staging; Steroids; Supplementation; Survival Rate; Tamoxifen; Testosterone; Time; Tumor Tissue; Vitamins; Woman; bone loss; chemotherapy; dietary supplements; flaxseed lignan; group intervention; hormone therapy; improved; interest; malignant breast neoplasm; outcome forecast; protein expression; steroid hormone; tumor

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.

描述（由申请人提供）：尽管早期乳腺癌女性的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改善其无复发生存期（RFS）的疗法感兴趣。芳香化酶抑制剂（AI）用于绝经后妇女，阻断雄激素向雌激素的外周转化，有效降低可促进乳腺肿瘤增殖的雌二醇。然而，使用人工智能与潮热、关节疼痛、骨质流失和心脏事件增加有关。此外，许多乳腺肿瘤最终会对激素治疗产生耐药性。补充和替代药物（CAM）被癌症幸存者广泛使用，试图减少疾病复发，副作用更少，潜在的健康益处，并且在乳腺癌幸存者中使用特别普遍。亚麻籽（FS）是一种常见的食物，通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，亚麻籽消耗已被证明表现出许多活动，表明亚麻籽在佐剂环境中的潜在益处。然而，大多数调查亚麻籽生物学效应的人类研究都涉及健康女性。关于乳腺癌妇女使用亚麻籽的有效性和安全性的临床数据很少，特别是在接受人工免疫的妇女中。由于亚麻籽中的植物雌激素可以影响许多受激素制剂影响的相同生物途径，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传导途径起作用，改变内分泌抗性的发展。亚麻籽和抗雌激素药物之间的潜在协同或拮抗作用特别令人感兴趣，因为越来越多地使用AI来治疗患有激素反应性疾病的绝经后妇女。我们建议在诊断为ER阳性乳腺癌的绝经后妇女中进行肿瘤活检和切除之间的2x2析因随机干预研究，以评估亚麻籽和AI对许多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Ki-67，caspase，ER α，ER β的肿瘤表达的潜在相互作用。、PgR、HER2、IGF1、IGFIR。术前设置提供了一个独特的机会，可以在短时间内快速获得与生长因子和肿瘤特征相关的信号通路相关的干预影响信息，而不受其他治疗的干扰。我们假设亚麻籽和AI干预将独立地有利地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凋亡。我们进一步假设，这些改善将反映在Mammostrat抗体组（Applied Genomics Incorporated）估计的改善的复发评分中。这项研究将为未来的膳食干预研究提供重要的临床数据，涉及植物雌激素木脂素从亚麻籽。拟议的研究计划检查亚麻籽消费的影响，一种富含植物雌激素的食物，与芳香酶抑制剂相比，作为治疗雌激素受体阳性乳腺癌的补充方法，以及亚麻籽和芳香酶抑制剂联合治疗对乳腺癌治疗的影响。由于越来越多地使用补充和替代治疗方法，以及芳香化酶抑制剂治疗乳腺癌，拟议的研究有可能提供有关植物雌激素含量高的食物对乳腺癌常用内分泌疗法的影响的重要临床信息。