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（由适用提供）：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，尤其是对于雌激素受体阳性女性而言。因此，乳腺癌的存活率对可能改善其无复发生存（RFS）的疗法感兴趣。用于绝经后妇女，芳香酶抑制剂（AI）阻止了雄激素向雌激素的周围转化，有效地降低了可用于促进乳腺肿瘤增殖的雌二醇。但是，AIS的使用与热闪烁，关节疼痛，骨丢失以及心脏事件增加有关。此外，许多乳腺肿瘤最终会产生对马疗法的抵抗力。癌症生存的互补和替代药物（CAM）被广泛使用，以减少疾病复发，而副作用较少，潜在的健康益处更少，并且在乳腺癌存活中使用尤其普遍。亚麻籽（FS）是一种常用的食物，通常作为饮食补充剂食用，并且是植物雌激素的木叶豆的最富有的食物。在实验模型中，已经显示出亚麻籽消耗表现出许多活动，这些活动表明在可调环境中亚麻籽具有潜在的好处。然而，大多数人类研究的生物学作用涉及健康的女性。关于乳腺癌女性，尤其是在接受AIS的患者中，临床数据缺乏有关亚麻籽使用的有效性和安全性。由于亚麻籽中的植物雌激素会影响受荷尔蒙剂影响的许多相同的生物学途径，因此可以进行饮食 - 药物相互作用。此外，亚麻籽可能会通过生长和信号通路作用，从而改变内分泌耐药性的发展。鉴于AIS越来越多地使用AIS治疗马酮反应性疾病的绝经后妇女，亚麻籽和抗雌激素之间的潜在协同或拮抗作用尤其令人感兴趣。我们建议在肿瘤活检和切除之间进行一项试验2x2阶乘随机干预研究，在绝经后妇女被诊断出患有ER乳腺癌阳性阳性的妇女中，以评估亚麻籽和AI对许多类固醇和肿瘤相关特征与长期生存相关的许多类固醇和肿瘤相关特征的影响，并研究了flaxseed和AI的潜在相互作用。 HER2，IGF1，IGFIR。手术前的环境提供了一个独特的机会，可以快速获取有关在短时间内与肿瘤特征有关的生长因子和信号途径相关影响的信息，而不会受到其他治疗的干扰。我们假设亚麻籽和AI干预措施都会独立影响生长因子和信号通路蛋白表达，从而导致肿瘤增殖减少和凋亡增加。我们进一步假设，这些改进将反映在由mammostrat抗体面板（Applied Genomics Incorporated）估计的改善复发评分中。拟议的研究将为未来的饮食干预研究提供重要的临床数据，该研究涉及亚麻籽的植物雌激素木脂蛋白。拟议的研究计划将亚麻籽消耗（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完整方法，以及联合亚麻籽和芳香酶抑制剂治疗对乳腺癌治疗的作用。由于越来越多地使用完成和替代方法的治疗方法，以及在乳腺癌治疗中的芳香酶抑制剂，因此拟议的研究可能提供有关植物雌激素高食物对植物雌激素中对乳腺癌常见内分泌疗法的影响的重要临床信息。