Effects of Antioxidant Supplementation during Breast Cancer Adjuvant Therapy

描述(由申请者提供)：这个K23指导的以患者为导向的研究职业发展奖的目标是发展Heather Greenlee，ND，PhD在乳腺癌辅助治疗期间使用抗氧化剂补充剂的安全性和有效性方面的专业知识。抗氧化剂补充剂在癌症放射治疗和化疗中的使用是有争议的，因为这种使用的短期和长期影响在很大程度上是未知的。例如，辅酶Q10(C0QIO)是一种脂溶抗氧化剂，已被假设可减少阿霉素引起的心脏毒性。然而，目前尚不清楚在阿霉素治疗期间使用辅酶Q10等抗氧化剂是否会降低阿霉素的长期疗效。尽管存在争议，估计有45%-80%的乳腺癌患者在治疗过程中使用抗氧化剂补充剂。需要精心设计的观察性研究和临床试验来阐明这些药物的效果。在这项拟议的奖项中，我将接受哥伦比亚大学医学中心资深研究人员在肿瘤学临床试验(Dawn Hershman，MD，MS)、氧化应激途径(Regina Santella，PhD)以及癌症预防和控制(Alfred Neugut，MD，PhD)领域的重点指导和培训。我将完成分子流行病学、生物统计学方法、临床试验设计以及癌症预防和控制方面的课程和培训。建议进行三项补充研究，以研究在乳腺癌辅助治疗期间使用抗氧化剂补充剂的早期和晚期影响。研究一是I期随机、安慰剂对照、药代动力学研究，研究C0QIO对乳腺癌治疗过程中阿霉素代谢的影响。第二项研究是Mb期随机安慰剂对照试验，研究C0QIO在乳腺癌治疗过程中预防阿霉素引起的心脏毒性的作用。研究三是路径研究中的嵌套队列研究，考察在乳腺癌化疗、放射治疗和激素治疗期间使用抗氧化剂补充剂对乳腺癌复发和存活率的影响。Path研究是一项由NCI资助的前瞻性队列研究，对象是在北加州Kaiser Permanente确诊的乳腺癌患者(n=3,000；PI：Lawrence Kushi，ScD)。在这项拟议的奖项完成后，我将成为一名独立研究员和使用临床试验和观察性研究的专家，以检验在乳腺癌治疗过程中使用抗氧化剂补充剂的短期和长期影响，并将为争取NCI R01资金做好充分准备。

DESCRIPTION (provided by applicant): The goal of this K23 Mentored Patient-Oriented Research Career Development Award is to develop Heather Greenlee, ND, PhD's expertise in the safety and efficacy of antioxidant supplement use during breast cancer adjuvant therapy. The use of antioxidant supplements during cancer radiation therapy and chemotherapy is controversial because the short- and long-term effects of this use are largely unknown. For example, coenzyme Q10 (C0QIO), a lipid soluble antioxidant, has been hypothesized to decrease doxorubicin-induced cardiotoxicity. However it is unknown if using an antioxidant supplement such as CoQ 10 during doxorubicin treatment would decrease doxorubicin's long-term treatment efficacy. Despite this controversy, an estimated 45-80% of breast cancer patients use antioxidant supplements during their treatment. Well designed observational studies and clinical trials are needed to elucidate the effects of these agents. In this proposed award, I will receive focused mentorship and training from established investigators at Columbia University Medical Center in the areas of oncology clinical trials (Dawn Hershman, MD, MS), pathways of oxidative stress (Regina Santella, PhD), and cancer prevention and control (Alfred Neugut, MD, PhD). I will complete coursework and training in molecular epidemiology, biostatistical methods, clinical trial design, and cancer prevention and control. Three complementary studies are proposed to study the early and late effects of antioxidant supplement use during adjuvant treatment for breast cancer. Study one is a phase I randomized, placebo-controlled, pharmacokinetic study on the effect of C0QIO on doxorubicin metabolism during breast cancer treatment. Study Two is a phase Mb randomized, placebo-controlled trial on the effect of C0QIO preventing doxorubicin-induced cardiotoxicity during breast cancer treatment. Study Three is a nested cohort study within the Pathways Study examining the effects of antioxidant supplement use during breast cancer chemotherapy, radiation therapy, and hormonal therapy on breast cancer recurrence and survival. The Pathways Study is an NCI-funded prospective cohort study of breast cancer patients diagnosed within Kaiser Permanente Northern California (n=3,000; PI: Lawrence Kushi, ScD). At the completion of this proposed award, I will be an independent researcher and expert in the use of clinical trials and observational studies to examine the short- and long-term effects of antioxidant supplement use during breast cancer treatment, and will be fully prepared to pursue NCI R01 funding.