K07 Preventive Oncology Academic Award

描述(申请人提供)：有效控制一种复杂的疾病，如乳腺癌，需要多学科的方法，弥合癌症病因的“为什么和什么”与预防癌症发病率、发病率和死亡率的“方法”之间的差距。这一预防肿瘤学学术奖将为候选人提供机会，以加强她在临床试验设计和生物统计学方面的技能，发展她在分子生物学、药理学和毒理学方面的知识，并赋予她必要的研究经验，以成功地将多学科方法整合到有效的化学预防策略的设计中。候选人将参加约翰霍普金斯大学和国家癌症研究所(NCI)提供的课程，重点是临床试验设计以及在流行病学和临床研究中使用生物标记物。她将参加流行病学系和肿瘤学中心的会议、巡回和研讨会。她还将从事与她的癌症预防活动相关的有限数量的教学和临床肿瘤学工作。为了与候选人精通干预试验的设计、实施和分析的目标保持一致，提出了两项临床研究，以检验西兰花芽或茶(BST)的水提取物作为乳腺癌化学预防药物的有效性。第一项研究通过进行为期两周的剂量发现临床试验，测量乳腺组织中第二相诱导剂活性和异硫氰酸酯代谢物，评估了西兰花芽茶在30名接受乳房缩小手术的健康女性中的药代动力学和药效学作用。在第二项研究中，将使用第二阶段随机试验设计，在126名乳腺癌风险增加的女性中，测试BST的3个月干预是否调节了一组特定的乳腺癌风险组织生物标志物，而不是安慰剂。这些计划中的发展经验，加上约翰霍普金斯大学的支持性环境和研究基础设施，以及凯西·赫尔兹苏尔博士和南希·戴维森博士的指导，将确保Visvanathan博士成功地转变为一名拥有化学预防试验专业知识的独立癌症预防和控制研究员。

DESCRIPTION (provided by applicant): Effective control of a complex disease such as breast cancer requires a multidisciplinary approach that bridges the gap between the "why and what" of cancer causation and the "how" to prevent cancer incidence morbidity and mortality. This Preventive Oncology Academic Award will provide the candidate the opportunity to strengthen her skills in clinical trial design and biostatistics, develop her knowledge in molecular biology, pharmacology and toxicology and give her the necessary research experience to successfully integrate a multidisciplinary approach into the design of effective chemoprevention strategies. The candidate will attend courses offered at Johns Hopkins as well as the National Cancer Institute (NCI) focusing on clinical trial design and the use of biomarkers in epidemiological and clinical research. She will participate in conferences, rounds and seminars both in the Department of Epidemiology and in the Oncology Center. She will also engage in a limited amount of teaching and clinical oncology work relevant to her cancer prevention activities. In keeping with the candidates goal to become proficient in the design, conduct and analysis of intervention trials two clinical studies are proposed to examine the efficacy of an aqueous extract of broccoli sprout or "tea" (BST) as a chemopreventive agent for breast cancer. The first study evaluates the pharmacokinetics and pharmacodynamic action of broccoli sprouts tea in 30 healthy women undergoing breast reduction surgery by conducting a two-week dose-finding clinical trial that measures both phase 2 inducer activity and isothiocyanate metabolites in mammary tissue. In the second study, a phase II randomized trial design will be used to test whether a 3 months intervention of BST modulates a panel of specific tissue biomarkers of breast cancer risk compared to placebo, in 126 women at increased risk for breast cancer. Together these planned developmental experiences along with the supportive environment and research infrastructure of Johns Hopkins and the mentorship of Dr Kathy Helzsouer and Dr Nancy Davidson will ensure Dr Visvanathan's successful transition into an independent cancer prevention and control investigator with expertise in chemoprevention trials.