Effects of Antioxidant Supplementation during Breast Cancer Adjuvant Therapy

描述（由申请人提供）：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石楠Greenlee，ND，博士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。在癌症放疗和化疗期间使用抗氧化剂补充剂是有争议的，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（CoQ 10），一种脂溶性抗氧化剂，已经被假设为降低阿霉素诱导的心脏毒性。然而，目前尚不清楚在多柔比星治疗期间使用抗氧化剂补充剂如辅酶Q10是否会降低多柔比星的长期治疗效果。尽管存在争议，但估计有45-80%的乳腺癌患者在治疗期间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作用。在这个提议的奖项中，我将从哥伦比亚大学医学中心的知名研究人员那里获得重点指导和培训，这些研究领域包括肿瘤学临床试验（Dawn Hershman，MD，MS），氧化应激途径（Regina Santella，PhD）和癌症预防和控制（Alfred Neugut，MD，PhD）。我将完成分子流行病学，生物统计方法，临床试验设计和癌症预防和控制方面的课程和培训。三个补充研究提出了研究早期和晚期的影响，抗氧化剂补充剂的使用在乳腺癌的辅助治疗。研究一是关于乳腺癌治疗期间C 0 Q10对阿霉素代谢的影响的I期随机、安慰剂对照、药代动力学研究。研究二是关于C 0 Q10在乳腺癌治疗期间预防多柔比星诱导的心脏毒性的作用的Mb期随机、安慰剂对照试验。研究3是Pathways研究中的一项嵌套队列研究，旨在检查乳腺癌化疗、放疗和激素治疗期间使用抗氧化剂补充剂对乳腺癌复发和生存的影响。路径研究是一项由NCI资助的前瞻性队列研究，在北方加州的Kaiser Permanente诊断的乳腺癌患者中进行（n= 3，000; PI：Lawrence Kushi，ScD）。在这个拟议的奖项完成后，我将是一个独立的研究人员和专家，在使用临床试验和观察性研究，以检查抗氧化剂补充剂在乳腺癌治疗期间使用的短期和长期影响，并将充分准备追求NCI R 01资金。相关性：大部分癌症患者在癌症治疗期间使用抗氧化剂补充剂。然而，这种使用的早期和晚期影响在很大程度上是未知的，并且可能是有害的。需要训练有素的调查人员在这一领域进行观察性研究和临床试验，以阐明这些药物的短期和长期影响。

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. RELEVANCE: A large proportion of cancer patients use antioxidant supplements during cancer treatment. However, the eariy and late effects of this use are largely unknown, and may be harmful. Well trained investigators are needed to conduct observational studies and clinical trials in this area to elucidate the short- and long-term effects of these agents.