Predictors of ovarian failure after chemotherapy in young breast cancer patients

年轻乳腺癌患者化疗后卵巢衰竭的预测因素

基本信息

批准号：
8514411
负责人：
Hui-Chun Irene Su
金额：
$ 11.58万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8514411
关键词：
10 year old Adjuvant Adjuvant Chemotherapy Age Aging American Antral Award Biological Markers Biological Preservation Blood Caliber Cancer Patient Cancer Prognosis Cancer Survivor Chemotherapy-Oncologic Procedure Clinical Cohort Studies Complex Counseling Cyclophosphamide Data Diagnosis Discipline Disease Enrollment Environmental Risk Factor Enzymes Fertility Follicle Stimulating Hormone Genetic Genetic Polymorphism Goals Hemorrhage Hormonal Human Image Learning Life Magnetic Resonance Imaging Malignant Neoplasms Measurement Measures Medical Menopause Mentors Methods Oocytes Operative Surgical Procedures Ovarian Ovary Patients Pattern Pelvis Pharmaceutical Preparations Physicians Physiology Premenopause Principal Investigator Process Reproduction Reproductive History Research Research Personnel Survivors Testing Time Ultrasonography Woman aged base cancer diagnosis cancer therapy chemotherapy cohort diaries fetal follow-up genetic epidemiology high risk indexing inhibin B interest malignant breast neoplasm mullerian-inhibiting hormone ovarian failure predictive modeling programs prospective reproductive reproductive epidemiology tool

项目摘要

Program Director/PrincipalInvestigator (Last, First, Middle): Su, H. Irene PROJECT SUMMARY (Seeinstructions): This mentored research award will prepare the candidate to become an independent investigator in reproductive epidemiology. Specifically, this proposal will enable the principal investigator to: 1) conduct a prospective cohort study; 2) learn methods in genetics epidemiology and predictive modeling; 3) collaborate with researchers multiple disciplines; and 4) gather data for an R01 submission. More than two million American women are breast cancer survivors. The large nu mber of reproductive aged women with breast cancer provides a unique opportunity to study the impact of this devastating disease and treatment on ovarian aging and reproduction. Accurately characterizing and predicting ovarian function in young breast cancer patients is an important issue to survivors because of implications on reproductive issues such as fertility and menopause and cancer survival. Current predictors of ovarian failure after chemotherapy are limited to age and chemotherapy regimen. The goal of this proposal is to identify significant hormonal, genetic and ovarian morphometric markers associated with ovarian failure after adjuvant chemotherapy. A 5-year prospective cohort study of pre- menopausal breast cancer patients, followed from diagnosis to post-chemotherapy, is proposed. We will test the hypotheses that: 1). Breast cancer patients with lower pre-chemotherapy anti-Mullerian hormone and inhibin B levels and higher pre-chemotherapy Follicle Stimulating Hormone levels will be more likely to develop ovarian failure after adjuvant chemotherapy; 2). Breast cancer patients with drug metabolizing enzyme polymorphisms resulting in higher cyclophosphamide exposure are more likely to develop ovarian failure after cyclophosphamide-based adjuvant chemotherapy; 3). Breast cancer patients with smaller pre- chemotherapy ovarian volume, diameter and antral follicle count, and larger changes in these measure- ments pre- and post-chemotherapy are more likely to develop ovarian failure; 4). A predictive index using variables from these aims can be derived to identify patients at high risk for ovarian failure after therapy. RELEVANCE (Seeinstructions): This study will identify hormonal, genetic and ovarian imaging markers to predict ovarian failure after chemotherapy. These tools will assist young breast cancer patients and their physicians in making treatment decisions that would impact cancer survival and reproduction.

项目总监/主要研究员（最后、第一、中间）：Su, H. Irene 项目摘要（参见说明）：该指导研究奖将为候选人成为独立调查员做好准备生殖流行病学。具体来说，该提案将使主要研究者能够：1）进行前瞻性队列研究； 2）学习遗传学流行病学和预测模型的方法； 3）协作与多个学科的研究人员合作； 4) 收集 R01 提交的数据。超过两百万美国女性是乳腺癌幸存者。大努患有乳腺癌的育龄妇女人数提供了一个独特的机会来研究乳腺癌的影响这种毁灭性的疾病和治疗对卵巢衰老和生殖的影响。准确地表征和预测年轻乳腺癌患者的卵巢功能对于幸存者来说是一个重要问题，因为对生育和更年期以及癌症生存等生殖问题的影响。当前的预测因素化疗后卵巢功能衰竭的发生受限于年龄和化疗方案。该提案的目标是确定重要的激素、遗传和卵巢形态标志物与辅助化疗后卵巢功能衰竭有关。一项为期 5 年的前瞻性队列研究建议对绝经期乳腺癌患者进行从诊断到化疗后的随访。我们将测试假设：1）。化疗前抗苗勒管激素水平较低的乳腺癌患者抑制素 B 水平和化疗前较高的卵泡刺激激素水平更有可能辅助化疗后出现卵巢功能衰竭； 2）。乳腺癌患者的药物代谢导致较高环磷酰胺暴露的酶多态性更有可能发展为卵巢以环磷酰胺为基础的辅助化疗后失败； 3）。乳腺癌患者体型较小化疗后卵巢体积、直径和窦卵泡计数，以及这些指标的较大变化- 化疗前和化疗后的情况更有可能发生卵巢功能衰竭； 4）。预测指数使用从这些目标中得出的变量可以用来识别治疗后卵巢功能衰竭高风险的患者。相关性（参见说明）：这项研究将确定激素、遗传和卵巢成像标记物，以预测卵巢功能衰竭化疗。这些工具将帮助年轻乳腺癌患者及其医生进行治疗影响癌症生存和繁殖的决定。