Predictors of Ovarian Function in Women Treated With Aromatase Inhibitors

使用芳香酶抑制剂治疗的女性卵巢功能的预测因素

• 批准号: 8303108
• 负责人: Norah Lynn Henry
• 金额: $ 17.26万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8303108
• 关键词: Ablation; Adjuvant; Adjuvant Chemotherapy; Aftercare; Age; Amenorrhea; Applications Grants; Aromatase Inhibitors; Biochemical; Biochemical Genetics; Breast; Breast Cancer Treatment; CYP2C19 gene; Cancer Patient; Chemicals; Chemotherapy-Oncologic Procedure; Clinical; Clinical Management; Clinical Research; Clinical Research Curriculum Award; Clinical Trials; Collaborations; Correlative Study; Cyclophosphamide; Cytochrome P450; Data; Environment; Enzymes; Epidemiologic Factors; Epidemiology; Estradiol; Estrogen Antagonists; Estrogen Therapy; Estrogens; Ethics; Failure; Family; Feedback; Follicle Stimulating Hormone; Frequencies; Funding; Generations; Genes; Genetic; Genetic Polymorphism; Genomics; Goals; Hormonal; Hormone Receptor; Hormones; Inhibin A; Instruction; Investigation; Knowledge; Lead; Maintenance; Master' s Degree; Menopause; Mentors; Mentorship; Michigan; Monitor; Morbidity - disease rate; Nucleotides; Ovarian; Ovarian Ablation; Ovariectomy; Ovary; Participant; Patients; Pharmacogenomics; Physicians; Population; Postmenopause; Premenopause; Recording of previous events; Recovery; Recovery of Function; Research; Research Design; Research Personnel; Research Project Grants; Research Proposals; Resort; Risk; Sampling; Series; Serological; Serum; Single Nucleotide Polymorphism; Staging; System; Tamoxifen; Time; Toxic effect; Training; Translations; Tumor Markers; United States; Universities; Woman; anastrozole; base; career; career development; chemotherapeutic agent; chemotherapy; cohort; deprivation; design; experience; high risk; hormone therapy; indexing; inhibin B; malignant breast neoplasm; mortality; mullerian-inhibiting hormone; oncology; programs; prospective; skills; tool; translational study

DESCRIPTION (provided by applicant): The purpose of this K07application is to provide the necessary training and environment to prepare the candidate to become an independent investigator, able to design, conduct, and acquire funding for high-quality clinical and translational studies that focus on endocrine therapy for breast cancer. During the proposed mentored period, career development activities will include (1) completion of a Masters Degree in Clinical Research Design and Statistical Analysis (K30 program), as well as additional didactic instruction in genetics, pharmacogenomics, and the ethics of genomic research, (2) mentorship by Dr. Daniel Hayes (an internationally recognized expert in breast cancer treatment and tumor marker analysis) in the design, execution, and interpretation of studies related to predictors of ovarian function during adjuvant aromatase inhibitor(AI) therapy for breast cancer, and (3) substantial collaboration with senior colleagues in the Consortium on Breast Cancer Pharmacogenomics and at the University of Michigan on pharmacogenomics, ovarian reserve, and the menopausal transition. The candidate proposes a research project that will focus on premenopausal women with early stage breast cancer who develop chemotherapy-induced ovarian failure (CIOF). These women likely would derive more benefit from estrogen deprivation with AI therapy than from tamoxifen, as has been demonstrated for postmenopausal women. However, a substantial percentage is likely to recover ovarian function during AI therapy due to LHRH feedback loops, which would render AI therapy ineffective. The cornerstone of this proposal is a prospective clinical trial of AI therapy in women with CIOF. The overall goal is to identify clinically applicable genetic, epidemiologic, and biochemical predictors of alterations of ovarian function during AI therapy using research samples and data collected from study participants. We hypothesize that we can predict which women will remain postmenopausal during AI therapy, and which are highly likely to recover ovarian function. The outlined career development program, along with the mentored research proposal for this K07 application, will augment the candidate's knowledge and research skills to enable the successful transition to an independent research career in clinical and translational breast oncology. RELEVANCE: Each year, approximately 20,000 premenopausal breast cancer patients in the U.S. receive chemotherapy and endocrine therapy. Aromatase inhibitor (AI) therapy may be preferable to tamoxifen, but may not be safe in all patients because of the potential for recovery of ovarian function. In this proposal we will identify those patients who can receive AI therapy safely, which will enable more personalized treatment decisions.

描述（由申请人提供）：此K07签署的目的是提供必要的培训和环境，以准备候选人成为独立的研究者，以设计，进行和获得资金，以用于侧重于乳腺癌内分泌治疗的高质量临床和翻译研究。 During the proposed mentored period, career development activities will include (1) completion of a Masters Degree in Clinical Research Design and Statistical Analysis (K30 program), as well as additional didactic instruction in genetics, pharmacogenomics, and the ethics of genomic research, (2) mentorship by Dr. Daniel Hayes (an internationally recognized expert in breast cancer treatment and tumor marker analysis) in the design, execution, and interpretation of studies related to predictors of乳腺癌辅助芳香酶抑制剂（AI）治疗期间的卵巢功能，以及（3）与财团的乳腺癌药物基因组学联盟和密歇根大学药物基因组学，卵巢储备和绝经过渡的高级同事的实质性合作。候选人提出了一项研究项目，该项目将重点放在患有早期乳腺癌的绝经前女性，这些妇女会产生化学疗法引起的卵巢衰竭（CIOF）。这些妇女可能会从AI疗法中获得雌激素剥夺比他莫昔芬的受益，这已经证明了绝经后妇女。但是，由于LHRH反馈回路，在AI治疗期间，很大一部分可能会恢复卵巢功能，这会使AI治疗无效。该提案的基石是对CIOF女性AI治疗的前瞻性临床试验。总体目标是使用研究参与者收集的研究样本和数据，确定卵巢功能变化的临床适用遗传，流行病学和生化预测指标。我们假设我们可以预测哪些女性在AI治疗期间将保持绝经后，并且哪些妇女很可能会恢复卵巢功能。概述的职业发展计划以及该K07应用程序的指导研究建议将增强候选人的知识和研究技能，以使成功过渡到临床和转化性乳房肿瘤学领域的独立研究职业。相关性：每年，美国大约有20,000名绝经前乳腺癌患者接受化学疗法和内分泌疗法。芳香酶抑制剂（AI）疗法可能比他莫昔芬更可取，但由于卵巢功能的恢复潜力，在所有患者中可能并不安全。在此提案中，我们将确定那些可以安全接受AI治疗的患者，这将实现更多个性化的治疗决定。